DNA damage resulting in multiple broken chromosomes

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby In human cells, both normal metabolic activities and environmental factors such as UV light and Radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell per day. Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. Ultraviolet ( UV) light is Electromagnetic radiation with a Wavelength shorter than that of Visible light, but longer than X-rays Radiation, as in Physics, is Energy in the form of waves or moving Subatomic particles emitted by an atom or other body as it changes from a higher energy A molecular lesion is damage to the structure of a Molecule that results in reduction or absence of normal function or in rare cases the gain of a new function ^[1] Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Transcription is the synthesis of RNA under the direction of DNA History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei Consequently, the DNA repair process is constantly active as it responds to damage in the DNA structure.

The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states:

1. an irreversible state of dormancy, known as senescence
2. cell suicide, also known as apoptosis or programmed cell death
3. unregulated cell division, which can lead to the formation of a tumor that is cancerous

The DNA repair ability of a cell is vital to the integrity of its genome and thus to its normal functioning and that of the organism. Senescence refers to the biological processes of a living Organism approaching an advanced age (i Programmed cell-death ( PCD) is death of a cell in any form mediated by an intracellular program See also Cancer A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells (termed neoplastic Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Many genes that were initially shown to influence lifespan have turned out to be involved in DNA damage repair and protection. ^[2] Failure to correct molecular lesions in cells that form gametes can introduce mutations into the genomes of the offspring and thus influence the rate of evolution. A gamete (from Ancient Greek γαμέτης; translated gamete = wife gametes = husband is a cell that fuses with another gamete eVolution is the third Album by eLDee, it was due to be released in 2008

DNA damage

DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day. Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. ^[1] While this constitutes only 0. 000165% of the human genome's approximately 6 billion bases (3 billion base pairs), unrepaired lesions in critical genes (such as tumor suppressor genes) can impede a cell's ability to carry out its function and appreciably increase the likelihood of tumor formation. A tumor suppressor gene, or antioncogene is a Gene that protects a cell from one step on the path to cancer See also Cancer A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells (termed neoplastic

The vast majority of DNA damage affects the primary structure of the double helix; that is, the bases themselves are chemically modified. In Biochemistry, the primary structure of a biological molecule is the exact specification of its atomic composition and the chemical bonds connecting those atoms (including These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. Unlike proteins and RNA, DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units In Biochemistry and Chemistry, the tertiary structure of a Protein or any other Macromolecule is its three-dimensional structure as defined DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage. In a "relaxed" double-helical segment of DNA, the two strands twist around the helical axis once every 10 In Biology, histones are the chief Protein components of Chromatin.

Sources of damage

DNA damage can be subdivided into two main types:

1. endogenous damage such as attack by reactive oxygen species produced from normal metabolic byproducts (spontaneous mutation), especially the process of oxidative deamination;
2. exogenous damage caused by external agents such as
   1. ultraviolet [UV 200-300nm] radiation from the sun
   2. other radiation frequencies, including x-rays and gamma rays
   3. hydrolysis or thermal disruption
   4. certain plant toxins
   5. human-made mutagenic chemicals, especially aromatic compounds that act as DNA intercalating agents
   6. cancer chemotherapy and radiotherapy

The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. The word endogenous means "arising from within" the opposite of Exogenous. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and Oxidative deamination is a form of Deamination that generates Oxoacids in the Liver. A nanometre ( American spelling: nanometer, symbol nm) ( Greek: νάνος nanos dwarf; μετρώ metrό count) is a Radiation, as in Physics, is Energy in the form of waves or moving Subatomic particles emitted by an atom or other body as it changes from a higher energy X-radiation (composed of X-rays) is a form of Electromagnetic radiation. Gamma rays (denoted as &gamma) are a form of Electromagnetic radiation or light emission of frequencies produced by sub-atomic particle interactions Hydrolysis is a Chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions which may go on to participate in further reactions Plants are living Organisms belonging to the kingdom Plantae. A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low In Biology, a mutagen ( Latin, literally origin of change) is a physical or chemical agent that changes the genetic information (usually DNA) In Chemistry, intercalation is the reversible inclusion of a Molecule (or group between two other molecules (or groups Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a back mutation, for example, through gene conversion). In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism Gene conversion is an event in DNA Genetic recombination, which occurs at high frequencies during meiotic division but which also occurs in somatic cells

Types of damage

There are four main types of damage to DNA due to endogenous cellular processes:

1. oxidation of bases [e. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state g. 8-oxo-7,8-dihydroguanine (8-oxoG)] and generation of DNA strand interruptions from reactive oxygen species,
2. alkylation of bases (usually methylation), such as formation of 7-methylguanine, 1-methyladenine, O6 methylguanine
3. hydrolysis of bases, such as deamination, depurination and depyrimidination. Alkylation is the transfer of an Alkyl group from one Molecule to another Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. Hydrolysis is a Chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions which may go on to participate in further reactions
4. mismatch of bases, due to errors in DNA replication, in which the wrong DNA base is stitched into place in a newly forming DNA strand, or a DNA base is skipped over or mistakenly inserted. DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules

Damage caused by exogenous agents comes in many forms. Some examples are:

1. UV-B light causes crosslinking between adjacent cytosine and thymine bases creating pyrimidine dimers. Ultraviolet ( UV) light is Electromagnetic radiation with a Wavelength shorter than that of Visible light, but longer than X-rays Pyrimidine dimers (cyclobutane dimer are pairs of Thymine and Cytosine bases in DNA that arise via Photochemical reactions Ultraviolet light This is called direct DNA damage. Direct DNA damage can occur when DNA directly absorbs the UV-B-photon
2. UV-A light creates mostly free radicals - especially if sunscreen penetrated into the skin. Ultraviolet ( UV) light is Electromagnetic radiation with a Wavelength shorter than that of Visible light, but longer than X-rays Sunscreen (also known as sunblock or suntan lotion) is a Lotion, spray or other Topical product that absorbs or reflects the Sun 's The damage caused by free radicals is called indirect DNA damage. Indirect DNA damage occurs when a UV-photon is absorbed in the human skin by a Chromophore that does not have the ability to convert the energy into
3. Ionizing radiation such as that created by radioactive decay or in cosmic rays causes breaks in DNA strands. Image talkNew_radiation_symbol_ISO_21482svg for details --> Ionizing radiation For the 1962 Bruce Conner film see Cosmic Ray (film Cosmic rays are energetic particles originating from space that impinge on
4. Thermal disruption at elevated temperature increases the rate of depurination (loss of purine bases from the DNA backbone) and single strand breaks. Depurination is a DNA alteration in which the hydrolysis of a Purine base (Adenine or Guanine from the Deoxyribose - Phosphate backbone occurs Purine ( 1) is a heterocyclic Aromatic Organic compound, consisting of a Pyrimidine ring fused to an Imidazole ring For example, hydrolytic depurination is seen in the thermophilic bacteria, which grow in hot springs at 85–250 °C. A thermophile is an organism &mdash a type of Extremophile &mdash which thrives at relatively high temperatures between 45 and 80 °C (113 and 176 °F A hot spring is a spring that is produced by the emergence of geothermally heated Groundwater from the earth's crust. ^[3] The rate of depurination (300 purine residues per genome per generation) is too high in these species to be repaired by normal repair machinery, hence a possibility of an adaptive response cannot be ruled out. Purine ( 1) is a heterocyclic Aromatic Organic compound, consisting of a Pyrimidine ring fused to an Imidazole ring Adaptive behavior is a type of Behavior that is used to adapt to another type of behavior or situation
5. Industrial chemicals such as vinyl chloride and hydrogen peroxide, and environmental chemicals such as polycyclic hydrocarbons found in smoke, soot and tar create a huge diversity of DNA adducts- ethenobases, oxidized bases, alkylated phosphotriesters and Crosslinking of DNA just to name a few. Crosslinks in DNA occur when various exogenous or endogenous agents react with two different positions in the DNA

UV damage, alkylation/methylation, X-ray damage and oxidative damage are examples of induced damage. Spontaneous damage can include the loss of a base, deamination, sugar ring puckering and tautomeric shift.

Nuclear versus mitochondrial DNA damage

In human cells, and eukaryotic cells in general, DNA is found in two cellular locations - inside the nucleus and inside the mitochondria. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. Nuclear DNA (nDNA) exists as chromatin during non-replicative stages of the cell cycle and is condensed into aggregate structures known as chromosomes during cell division. Chromatin is the complex basis of DNA and protein that makes up Chromosomes It is found inside the nuclei of eukaryotic cells, and within the The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication A chromosome is an organized structure of DNA and Protein that is found in cells. Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells. In either state the DNA is highly compacted and wound up around bead-like proteins called histones. In Biology, histones are the chief Protein components of Chromatin. Whenever a cell needs to express the genetic information encoded in its nDNA the required chromosomal region is unravelled, genes located therein are expressed, and then the region is condensed back to its resting conformation. Mitochondrial DNA (mtDNA) is located inside mitochondria organelles, exists in multiple copies, and is also tightly associated with a number of proteins to form a complex known as the nucleoid. In Cell biology, an organelle (pronunciation /ɔː(rgəˡnɛl/ is a specialized subunit within a cell that has a specific function and is usually separately enclosed Inside mitochondria, reactive oxygen species (ROS), or free radicals, byproducts of the constant production of adenosine triphosphate (ATP) via oxidative phosphorylation, create a highly oxidative environment that is known to damage mtDNA. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Oxidative phosphorylation is a Metabolic pathway that uses energy released by the oxidation of Nutrients to produce Adenosine triphosphate (ATP A critical enzyme in counteracting the toxicity of these species is superoxide dismutase, which is present in both the mitochondria and cytoplasm of eukaryotic cells. The enzyme superoxide dismutase ( SOD,) catalyzes the Dismutation of Superoxide into Oxygen and Hydrogen peroxide. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane.

Senescence and apoptosis

Senescence, an irreversible state in which the cell no longer divides (mitosis), is a protective response to the shortening of the chromosome ends (telomeres). Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei A telomere is a region of repetitive DNA at the end of Chromosomes which protects the end of the chromosome from destruction The telomeres are long regions of repetitive noncoding DNA that cap chromosomes and undergo partial degradation each time a cell undergoes division (see Hayflick limit). In Genetics, non-coding DNA describes DNA which does not contain instructions for making Proteins (or other cell products such as Noncoding The Hayflick limit is the number of times a cell will divide before it stops due to the telomere reaching a critical length. ^[4] In contrast, quiescence is a reversible state of cellular dormancy that is unrelated to genome damage (see cell cycle). The G0 phase (G sub 0 is a period in the Cell cycle where cells exist in a quiescent state The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication Senescence in cells may serve as a functional alternative to apoptosis in cases where the physical presence of a cell for spatial reasons is required by the organism,^[5] which serves as a "last resort" mechanism to prevent a cell with damaged DNA from replicating inappropriately in the absence of pro-growth cellular signaling. Cell signaling is part of a Complex system of Communication that governs basic cellular activities and coordinates cell actions Unregulated cell division can lead to the formation of a tumor (see cancer), which is potentially lethal to an organism. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Therefore the induction of senescence and apoptosis is considered to be part of a strategy of protection against cancer.

DNA damage and mutation

It is important to distinguish between DNA damage and mutation, the two major types of error in DNA. DNA damages and mutation are fundamentally different. Damages are physical abnormalities in the DNA, such as single and double strand breaks, 8-hydroxydeoxyguanosine residues and polycyclic aromatic hydrocarbon adducts. DNA damages can be recognized by enzymes, and thus they can be correctly repaired if redundant information, such as the undamaged sequence in the complementary DNA strand or in a homologous chromosome, is available for copying. If a cell retains DNA damage, transcription of a gene can be prevented and thus translation into a protein will also be blocked. Replication may also be blocked and/or the cell may die.

In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and regulation. Mutations are replicated when the cell replicates. In a population of cells, mutant cells will increase or decrease in frequency according to the effects of the mutation on the ability of the cell to survive and reproduce. Although distinctly different from each other, DNA damages and mutations are related because DNA damages often cause errors of DNA synthesis during replication or repair and these errors are a major source of mutation.

Given these properties of DNA damage and mutation, it can be seen that DNA damages are a special problem in non-dividing or slowly dividing cells, where unrepaired damages will tend to accumulate over time. On the other hand, in rapidly dividing cells, unrepaired DNA damages that do not kill the cell by blocking replication will tend to cause replication errors and thus mutation. The great majority of mutations that are not neutral in their effect are deleterious to a cell’s survival. Thus, in a population of cells comprising a tissue with replicating cells, mutant cells will tend to be lost. However infrequent mutations that provide a survival advantage will tend to clonally expand at the expense of neighboring cells in the tissue. This advantage to the cell is disadvantageous to the whole organism, because such mutant cells can give rise to cancer. Thus DNA damages in frequently dividing cells, because they give rise to mutations, are a prominent cause of cancer. In contrast, DNA damages in infrequently dividing cells are likely a prominent cause of aging.

DNA repair mechanisms

Single strand and double strand DNA damage

Cells cannot function if DNA damage corrupts the integrity and accessibility of essential information in the genome (but cells remain superficially functional when so-called "non-essential" genes are missing or damaged). In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby Depending on the type of damage inflicted on the DNA's double helical structure, a variety of repair strategies have evolved to restore lost information. If possible, cells use the unmodified complementary strand of the DNA or the sister chromatid as a template to losslessly recover the original information. A chromatid is one of two identical copies of DNA making up a replicated Chromosome, which are joined at their Centromeres for the process of Cell division Without access to a template, cells use an error-prone recovery mechanism known as translesion synthesis as a last resort.

Damage to DNA alters the spatial configuration of the helix and such alterations can be detected by the cell. Once damage is localized, specific DNA repair molecules bind at or near the site of damage, inducing other molecules to bind and form a complex that enables the actual repair to take place. The types of molecules involved and the mechanism of repair that is mobilized depend on the type of damage that has occurred and the phase of the cell cycle that the cell is in. The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication

Direct reversal

Cells are known to eliminate three types of damage to their DNA by chemically reversing it. These mechanisms do not require a template, since the types of damage they counteract can only occur in one of the four bases. Such direct reversal mechanisms are specific to the type of damage incurred and do not involve breakage of the phosphodiester backbone. The formation of thymine dimers (a common type of cyclobutyl dimer) upon irradiation with UV light results in an abnormal covalent bond between adjacent thymidine bases. A thymine dimer is the covalent bonding of two adjacent Thymine residues within a DNA molecule often catalyzed by ultraviolet radiation or chemical mutagenic agents Pyrimidine dimers (cyclobutane dimer are pairs of Thymine and Cytosine bases in DNA that arise via Photochemical reactions Ultraviolet light The photoreactivation process directly reverses this damage by the action of the enzyme photolyase, whose activation is obligately dependent on energy absorbed from blue/UV light (300–500nm wavelength) to promote catalysis. Photolyase is an Enzyme that binds complementary DNA strands and breaks certain types of Pyrimidine dimers that are caused by exposure to Ultraviolet light Photolyase is an Enzyme that binds complementary DNA strands and breaks certain types of Pyrimidine dimers that are caused by exposure to Ultraviolet light The electromagnetic (EM spectrum is the range of all possible Electromagnetic radiation frequencies In Physics wavelength is the distance between repeating units of a propagating Wave of a given Frequency. ^[6] Another type of damage, methylation of guanine bases, is directly reversed by the protein methyl guanine methyl transferase (MGMT), the bacterial equivalent of which is called as ogt. O6-alkyl guanine transferase II ( O6 AGT II) previously known as O6 Guanine transferase ( ogt) is also part of the DNA This is an expensive process because each MGMT molecule can only be used once; that is, the reaction is stoichiometric rather than catalytic. Stoichiometry (sometimes called reaction stoichiometry to distinguish it from composition stoichiometry is the Calculation of Quantitative (measurable Catalysis is the process in which the rate of a Chemical reaction is increased by means of a Chemical substance known as a catalyst ^[7] A generalized response to methylating agents in bacteria is known as the adaptive response and confers a level of resistance to alkylating agents upon sustained exposure by upregulation of alkylation repair enzymes. The adaptive response is a form of direct DNA repair in E coli that is initiated against Alkylation, particularly Methylation, of ^[8] The third type of DNA damage reversed by cells is certain methylation of the bases cytosine and adenine.

Single strand damage

Structure of the base-excision repair enzyme uracil-DNA glycosylase. DNA glycosylases are a family of Enzymes involved in Base excision repair, classified under EC number EC 3 The uracil residue is shown in yellow.

When only one of the two strands of a double helix has a defect, the other strand can be used as a template to guide the correction of the damaged strand. In order to repair damage to one of the two paired molecules of DNA, there exist a number of excision repair mechanisms that remove the damaged nucleotide and replace it with an undamaged nucleotide complementary to that found in the undamaged DNA strand. ^[7]

1. Base excision repair (BER), which repairs damage to a single nucleotide caused by oxidation, alkylation, hydrolysis, or deamination. Base excision repair (BER is a cellular mechanism that repairs damaged DNA throughout the cell cycle The base is removed with glycosylase and ultimately replaced by repair synthesis with DNA ligase.
2. Nucleotide excision repair (NER), which repairs damage affecting longer strands of 2–30 bases. Nucleotide excision repair is a DNA repair mechanism DNA constantly requires repair due to damage that can occur to bases from a vast variety of sources including This process recognizes bulky, helix-distorting changes such as thymine dimers as well as single-strand breaks (repaired with enzymes such UvrABC endonuclease). A thymine dimer is the covalent bonding of two adjacent Thymine residues within a DNA molecule often catalyzed by ultraviolet radiation or chemical mutagenic agents UvrABC endonuclease is a multienzyme complex in Ecoli bacteria involved in DNA repair mechanism by Nucleotide excision repair and it is therefore sometimes A specialized form of NER known as Transcription-Coupled Repair (TCR) deploys high-priority NER repair enzymes to genes that are being actively transcribed. Transcription-coupled repair is a DNA repair mechanism which operates in tandem with transcription. Transcription is the synthesis of RNA under the direction of DNA
3. Mismatch repair (MMR), which corrects errors of DNA replication and recombination that result in mispaired (but normal, that is non- damaged) nucleotides following DNA replication. DNA mismatch repair is a system for recognising and repairing erroneous insertion deletion and mis-incorporation of bases that can arise during DNA replication and recombination DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules Genetic recombination is the process by which a strand of genetic material (usually DNA; but can also be RNA) is broken and then joined to a different DNA molecule
   

Double-strand breaks

Double-strand breaks (DSBs), in which both strands in the double helix are severed, are particularly hazardous to the cell because they can lead to genome rearrangements. Two mechanisms exist to repair DSBs: non-homologous end joining (NHEJ) and recombinational repair (also known as template-assisted repair or homologous recombination repair). Non-homologous end joining ( NHEJ) is a pathway that repairs double-strand breaks in DNA Genetic recombination is the process by which a strand of genetic material (usually DNA; but can also be RNA) is broken and then joined to a different DNA molecule ^[7]

DNA ligase, shown above repairing chromosomal damage, is an enzyme that joins broken nucleotides together by catalyzing the formation of an internucleotide ester bond between the phosphate backbone and the deoxyribose nucleotides. Esters are a class of Chemical compounds and Functional groups Esters consist of an inorganic or organic Acid in which at least

In NHEJ, DNA Ligase IV, a specialized DNA Ligase that forms a complex with the cofactor XRCC4, directly joins the two ends. In Molecular biology, DNA ligase is a special type of Ligase ( that can link together two DNA strands that have single-strand breaks (a break in both complementary X-ray repair complementing defective repair in Chinese hamster cells 4, also known as XRCC4, is a human Gene. ^[9] To guide accurate repair, NHEJ relies on short homologous sequences called microhomologies present on the single-stranded tails of the DNA ends to be joined. If these overhangs are compatible, repair is usually accurate. ^{[10][11][12][13]} NHEJ can also introduce mutations during repair. Loss of damaged nucleotides at the break site can lead to deletions, and joining of nonmatching termini forms translocations. NHEJ is especially important before the cell has replicated its DNA, since there is no template available for repair by homologous recombination. There are "backup" NHEJ pathways in higher eukaryotes. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex ^[14] Besides its role as a genome caretaker, NHEJ is required for joining hairpin-capped double-strand breaks induced during V(D)J recombination, the process that generates diversity in B-cell and T-cell receptors in the vertebrate immune system. V(DJ recombination is a mechanism of Genetic recombination that occurs in Vertebrates which randomly selects and assembles segments of Genes encoding Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells that is in general responsible for recognizing Antigens bound Vertebrates are members of the Subphylum Vertebrata, Chordates with backbones or spinal columns The grouping sometimes includes An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor ^[15]

Recombinational repair requires the presence of an identical or nearly identical sequence to be used as a template for repair of the break. The enzymatic machinery responsible for this repair process is nearly identical to the machinery responsible for chromosomal crossover during meiosis. This pathway allows a damaged chromosome to be repaired using a sister chromatid (available in G2 after DNA replication) or a homologous chromosome as a template. A chromatid is one of two identical copies of DNA making up a replicated Chromosome, which are joined at their Centromeres for the process of Cell division DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules Homologous chromosomes are Chromosomes in a Biological cell that pair ( synapse) during Meiosis, or alternatively non-identical chromosomes that DSBs caused by the replication machinery attempting to synthesize across a single-strand break or unrepaired lesion cause collapse of the replication fork and are typically repaired by recombination. The replication fork is a structure that forms during DNA replication.

Topoisomerases introduce both single- and double-strand breaks in the course of changing the DNA's state of supercoiling, which is especially common in regions near an open replication fork. Topoisomerases (type I, type II) are Isomerase Enzymes that act on the topology of DNA. In a "relaxed" double-helical segment of DNA, the two strands twist around the helical axis once every 10 Such breaks are not considered DNA damage because they are a natural intermediate in the topoisomerase biochemical mechanism and are immediately repaired by the enzymes that created them.

A team of French researchers bombarded Deinococcus radiodurans to study the mechanism of double-strand break DNA repair in that organism. Deinococcus radiodurans is an extremophilic Bacterium, one of the most Radioresistant organisms known At least two copies of the genome, with random DNA breaks, can form DNA fragments through annealing. Annealing, in Genetics, means for DNA or RNA to pair by Hydrogen bonds to a complementary sequence, forming a double-stranded Partially overlapping fragments are then used for synthesis of homologous regions through a moving D-loop that can continue extension until they find complementary partner strands. In Evolutionary biology, homology has come to mean any similarity between characters that is due to their shared ancestry. In Molecular biology, a displacement loop or D-loop is a DNA structure where the two strands of a double-stranded DNA molecule are separated for a stretch In the final step there is crossover by means of RecA-dependent homologous recombination. RecA is a 38 kilodalton Escherichia coli Protein essential for the repair and maintenance of DNA. ^[16]

Translesion synthesis

Translesion synthesis is a DNA damage tolerance process that allows the DNA replication machinery to replicate past DNA lesions such as thymine dimers or AP sites. DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules A thymine dimer is the covalent bonding of two adjacent Thymine residues within a DNA molecule often catalyzed by ultraviolet radiation or chemical mutagenic agents It involves the switching out of regular DNA polymerases for specialized translesion polymerases, often with larger active sites that can facilitate the insertion of bases opposite damaged nucleotides. A DNA Polymerase is an Enzyme that assists in DNA replication. The polymerase switching is thought to be mediated by, among other factors, the post-translational modification of the replication processivity factor PCNA. In Molecular biology, processivity is a measure of the average number of Nucleotides added by a DNA polymerase Enzyme per association/disassociation Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a Protein that acts as a Processivity factor for DNA polymerase delta in Translesion synthesis polymerases often have low fidelity (high propensity to insert wrong bases) relative to regular polymerases. However, many are extremely efficient at inserting correct bases opposite specific types of damage. For example, Pol η mediates error-free bypass of lesions induced by UV irradiation, whereas Pol ζ introduces mutations at these sites. DNA polymerase eta ( Pol η) is a eukaryotic DNA polymerase involved in the DNA repair by translesion synthesis. Ultraviolet ( UV) light is Electromagnetic radiation with a Wavelength shorter than that of Visible light, but longer than X-rays From a cellular perspective, risking the introduction of point mutations during translesion synthesis may be preferable to resorting to more drastic mechanisms of DNA repair, which may cause gross chromosomal aberrations or cell death. A point mutation, or single base substitution, is a type of Mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic

Global response to DNA damage

Cells exposed to ionizing radiation, ultraviolet light or chemicals are prone to acquire multiple sites of bulky DNA lesions and double strand breaks. Image talkNew_radiation_symbol_ISO_21482svg for details --> Ionizing radiation Ultraviolet ( UV) light is Electromagnetic radiation with a Wavelength shorter than that of Visible light, but longer than X-rays Moreover, DNA damaging agents can damage other biomolecules such as proteins, carbohydrates, lipids and RNA. A biomolecule is any organic Molecule that is produced by living Organisms including large Polymeric molecules such as Proteins Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Carbohydrates (from ' Hydrates of Carbon ' or saccharides ( Greek σάκχαρον meaning " Sugar " are the most Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units The accumulation of damage, specifically double strand breaks or adducts stalling the replication forks, are among known stimulation signals for a global response to DNA damage. The replication fork is a structure that forms during DNA replication. ^[17] The global response to damage is an act directed toward the cells' own preservation and triggers multiple pathways of macromolecular repair, lesion bypass, tolerance or apoptosis. The common features of global response are induction of multiple genes, cell cycle arrest, and inhibition of cell division. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells.

DNA damage checkpoints

After DNA damage, cell cycle checkpoints are activated. The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication Cell cycle checkpoints are control mechanisms that ensure the fidelity of cell division in Eukaryotic cells. Checkpoint activation pauses the cell cycle and gives the cell time to repair the damage before continuing to divide. DNA damage checkpoints occur at the G1/S and G2/M boundaries. The G1 phase is a period in the Cell cycle during Interphase, after Cytokinesis and before the S phase. The S phase, short for synthesis phase, is a period in the Cell cycle during Interphase, between G1 phase and the G2 phase. G2 phase is the third final and usually the shortest subphase during interphase within the Cell cycle in which the cell undergoes a period of rapid growth to prepare Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei An intra-S checkpoint also exists. The S phase, short for synthesis phase, is a period in the Cell cycle during Interphase, between G1 phase and the G2 phase. Checkpoint activation is controlled by two master kinases, ATM and ATR. In Chemistry and Biochemistry, a kinase, alternatively known as a phosphotransferase, is a type of Enzyme that transfers Phosphate Ataxia telangiectasia mutated (ATM is a Serine / Threonine -specific Protein kinase ( that is recruited and activated by DNA double-strand breaks Ataxia telangiectasia and Rad3 related (ATR is a Serine / Threonine -specific Protein kinase that is involved in sensing DNA damage and activating ATM responds to DNA double-strand breaks and disruptions in chromatin structure,^[18] whereas ATR primarily responds to stalled replication forks. The replication fork is a structure that forms during DNA replication. These kinases phosphorylate downstream targets in a signal transduction cascade, eventually leading to cell cycle arrest. Phosphorylation is the addition of a Phosphate (PO4 group to a Protein molecule or a small molecule In Biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another A class of checkpoint mediator proteins including BRCA1, MDC1, and 53BP1 has also been identified. BRCA1 ( Breast cancer 1 early onset is a Human Gene, some mutations of which are associated with a significant increase in the risk of Breast cancer Mediator of DNA damage checkpoint 1, also known as MDC1, is a human Gene. ^[19] These proteins seem to be required for transmitting the checkpoint activation signal to downstream proteins.

p53 is an important downstream target of ATM and ATR, as it is required for inducing apoptosis following DNA damage. p53 (also known as protein 53 or tumor protein 53) is a Transcription factor encoded by the TP53 gene ^[20] At the G1/S checkpoint, p53 functions by deactivating the CDK2/cyclin E complex. Cyclin E is a member of the Cyclin family Cyclin E binds to G1 phase Cdk2 which is required for the transition from G1 to S phase Similarly, p21 mediates the G2/M checkpoint by deactivating the CDK1/cyclin B complex. Cyclin-dependent kinase inhibitor 1A (p21 Cip1, also known as CDKN1A, is a human Gene. Cell division cycle 2 G1 to S and G2 to M, also known as Cdk1 (CDC2, is a human Gene. Cyclin B is a member of the Cyclin family Cyclin B is a mitotic cyclin

The prokaryotic SOS response

The SOS response is the term used to describe changes in gene expression in Escherichia coli and other bacteria in response to DNA damage. The SOS response is a postreplication DNA repair system that allows DNA replication to bypass lesions or errors in the DNA. Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such The prokaryotic SOS system is regulated by two key proteins: LexA and RecA. The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other Repressor LexA or LexA is a Repressor Enzyme ( that represses SOS response Genes coding for DNA polymerases required for RecA is a 38 kilodalton Escherichia coli Protein essential for the repair and maintenance of DNA. The LexA homodimer is a transcriptional repressor that binds to operator sequences commonly referred to as SOS boxes. A dimer is a Chemical or Biological entity consisting of two subunits called Monomers which are held together by either Intramolecular forces Transcription is the synthesis of RNA under the direction of DNA For other uses see Repression A repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing In Mathematics, an operator is a function which operates on (or modifies another function It is known that LexA regulates transcription of approximately 48 genes including the lexA and recA genes. ^[21] The most common cellular signals activating the SOS response are regions of single stranded DNA (ssDNA), arising from stalled replication forks or double strand breaks, which are processed by DNA helicase to separate the two DNA strands. The replication fork is a structure that forms during DNA replication. Helicases are a class of Enzymes vital to all living Organisms They are motor proteins that move directionally along a Nucleic acid phosphodiester backbone ^[17] Once the DNA damage is repaired or bypassed using polymerases or through recombination, the amount of single-stranded DNA in cells is decreased, lowering the amounts of RecA filaments decreases cleavage activity of LexA homodimer which subsequently binds to the SOS boxes near promoters and restores normal gene expression.

Eukaryotic transcriptional responses to DNA damage

Eukaryotic cells exposed to DNA damaging agents also activate important defensive pathways by inducing multiple proteins involved in DNA repair, cell cycle checkpoint control, protein trafficking and degradation. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex Cell cycle checkpoints are control mechanisms that ensure the fidelity of cell division in Eukaryotic cells. Such genome wide transcriptional response is very complex and tightly regulated, thus allowing coordinated global response to damage. Exposure of yeast Saccharomyces cerevisiae to DNA damaging agents results in overlapping but distinct transcriptional profiles. Yeasts are a growth form of eukaryotic Microorganisms classified in the kingdom Fungi, with about 1500 Species currently described Saccharomyces cerevisiae is a Species of Budding Yeast. It is perhaps the most useful Yeast owing to its use since ancient times Similarities to environmental shock response indicates that a general global stress response pathway exist at the level of transcriptional activation. A Shock Response Spectrum (SRS is a graphical representation of an arbitrary transient acceleration input such as shock in terms of how a Single Degree Of Freedom In contrast, different human cell types respond to damage differently indicating an absence of a common global response. The probable explanation for this difference between yeast and human cells may be in the heterogeneity of mammalian cells. Heterogeneous is an adjective used to describe an object or system consisting of multiple items having a large number of structural variations Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands In an animal different types of cells are distributed amongst different organs which have evolved different sensitivities to DNA damage. ^[22]

In general global response to DNA damage involves expression of multiple genes responsible for postreplication repair, homologous recombination, nucleotide excision repair, DNA damage checkpoint, global transcriptional activation, genes controlling mRNA decay and many others. Postreplication Repair (PRR DNA damage prevents the normal enzymatic synthesis of DNA by the Replication fork. Postreplication Checkpoint When the genomic DNA of eukaryotic cells becomes damaged by spontaneous processes chemical mutagens or sunlight exposure the replication of damaged The vast amount of damage to a cell leaves it with an important decision; undergo apoptosis and die, or survive at the cost of living with a modified genome. An increase in tolerance to damage can lead to an increased rate of survival which will allow a greater accumulation of mutations. Yeast Rev1 and human polymerase η are members of [Y family translesion DNA polymerases present during global response to DNA damage and are responsible for enhanced mutagenesis during a global response to DNA damage in eukaryotes. A polymerase (EC 2776/7/19/48/49 is an Enzyme whose central function is associated with Polymers of Nucleic acids such as RNA and DNA ^[17]

DNA repair and aging

Pathological effects of poor DNA repair

DNA repair rate is an important determinant of cell pathology

Experimental animals with genetic deficiencies in DNA repair often show decreased lifespan and increased cancer incidence. For example, mice deficient in the dominant NHEJ pathway and in telomere maintenance mechanisms get lymphoma and infections more often, and consequently have shorter lifespans than wild-type mice. Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system) ^[23] Similarly, mice deficient in a key repair and transcription protein that unwinds DNA helices have premature onset of aging-related diseases and consequent shortening of lifespan. ^[24] However, not every DNA repair deficiency creates exactly the predicted effects; mice deficient in the NER pathway exhibited shortened lifespan without correspondingly higher rates of mutation. ^[25]

If the rate of DNA damage exceeds the capacity of the cell to repair it, the accumulation of errors can overwhelm the cell and result in early senescence, apoptosis or cancer. Inherited diseases associated with faulty DNA repair functioning result in premature aging, increased sensitivity to carcinogens, and correspondingly increased cancer risk (see below). DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its Genome. On the other hand, organisms with enhanced DNA repair systems, such as Deinococcus radiodurans, the most radiation-resistant known organism, exhibit remarkable resistance to the double strand break-inducing effects of radioactivity, likely due to enhanced efficiency of DNA repair and especially NHEJ. Deinococcus radiodurans is an extremophilic Bacterium, one of the most Radioresistant organisms known Radioactive decay is the process in which an unstable Atomic nucleus loses energy by emitting ionizing particles and Radiation. ^[26] It is noteworthy that some works suggest that if a DNA damage event occurs during the self repair process then the combination of the two events will exert an effect greater than the sum of the individual events (if they occurred with a long time delay between them), this is the basis of the second event theory favoured by C. Busby (The Low Level Radiation Campaign).

Longevity and caloric restriction

Most lifespan influencing genes affect the rate of DNA damage

A number of individual genes have been identified as influencing variations in lifespan within a population of organisms. The effects of these genes is strongly dependent on the environment, particularly on the organism's diet. Caloric restriction reproducibly results in extended lifespan in a variety of organisms, likely via nutrient sensing pathways and decreased metabolic rate. Calorie restriction, or caloric restriction (CR aims to improve health and slow the aging process by limiting dietary energy intake Nutrient sensing is a cell's ability to recognize and respond to fuel substrates such as Glucose. Basal metabolic rate ( BMR) is the amount of energy expended while at rest in a neutrally temperate environment in the post-absorptive state (meaning that the digestive system The molecular mechanisms by which such restriction results in lengthened lifespan are as yet unclear (see^[27] for some discussion); however, the behavior of many genes known to be involved in DNA repair is altered under conditions of caloric restriction.

For example, increasing the gene dosage of the gene SIR-2, which regulates DNA packaging in the nematode worm Caenorhabditis elegans, can significantly extend lifespan. Gene dosage is the number of copies of a Gene present in a cell or nucleus. The nematodes or roundworms ( Phylum Nematoda from Greek (nema "thread" + -ode "like" are one of the most common ^[28] The mammalian homolog of SIR-2 is known to induce downstream DNA repair factors involved in NHEJ, an activity that is especially promoted under conditions of caloric restriction. ^[29] Caloric restriction has been closely linked to the rate of base excision repair in the nuclear DNA of rodents,^[30] although similar effects have not been observed in mitochondrial DNA. ^[31]

Interestingly, the C. elegans gene AGE-1, an upstream effector of DNA repair pathways, confers dramatically extended lifespan under free-feeding conditions but leads to a decrease in reproductive fitness under conditions of caloric restriction. ^[32] This observation supports the pleiotropy theory of the biological origins of aging, which suggests that genes conferring a large survival advantage early in life will be selected for even if they carry a corresponding disadvantage late in life. Pleiotropy occurs when a single Gene influences multiple phenotypic traits Consequently a new Mutation in the gene will have an effect on all Senescence refers to the biological processes of a living Organism approaching an advanced age (i

Medicine and DNA repair modulation

Hereditary DNA repair disorders

Defects in the NER mechanism are responsible for several genetic disorders, including:

• xeroderma pigmentosum: hypersensitivity to sunlight/UV, resulting in increased skin cancer incidence and premature aging
• Cockayne syndrome: hypersensitivity to UV and chemical agents
• trichothiodystrophy: sensitive skin, brittle hair and nails

Mental retardation often accompanies the latter two disorders, suggesting increased vulnerability of developmental neurons. Xeroderma pigmentosum, or XP is an Autosomal recessive Genetic disorder of DNA repair in which the ability to repair damage caused by Ultraviolet Cockayne syndrome (also called Weber -Cockayne syndrome, or Neill-Dingwall Syndrome) is a rare Autosomal Recessive Congenital Trichothiodystrophy is a rare genetic condition caused by mutations in either of the ERCC2/XPD and ERCC3/XPB genes

Other DNA repair disorders include:

• Werner's syndrome: premature aging and retarded growth
• Bloom's syndrome: sunlight hypersensitivity, high incidence of malignancies (especially leukemias). Werner Syndrome (WRN is a very rare autosomal recessive disorder characterized by the appearance of premature aging. Bloom syndrome (BLM is a rare Autosomal Recessive chromosomal disorder characterized by a high frequency of breaks and rearrangements in an affected person's Malignant (from the Latin roots mal- = "bad" and -genus = "born" is a medical term used to describe a severe and progressively worsening disease Leukemia or leukaemia (Greek leukos λευκός, "white" aima αίμα, "blood" is a Cancer of the Blood
• ataxia telangiectasia: sensitivity to ionizing radiation and some chemical agents

All of the above diseases are often called "segmental progerias" ("accelerated aging diseases") because their victims appear elderly and suffer from aging-related diseases at an abnormally young age. Ataxia-telangiectasia (AT ( Boder-Sedgwick syndrome or Louis-Bar syndrome) is a rare neurodegerative inherited disease which affects many parts of the body Progeria is a condition of early aging which usually refers specifically to Hutchinson-Gilford Progeria syndrome. An DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair.

Other diseases associated with reduced DNA repair function include Fanconi's anemia, hereditary breast cancer and hereditary colon cancer. Fanconi anemia (FA is a genetic disease that affects children and adults from all ethnic backgrounds Breast cancer is a Cancer that starts in the cells of the Breast in women and men Colorectal cancer, also called colon cancer or large bowel cancer, includes Cancerous growths in the colon, Rectum and

DNA repair and cancer

Inherited mutations that affect DNA repair genes are strongly associated with high cancer risks in humans. Hereditary nonpolyposis colorectal cancer (HNPCC) is strongly associated with specific mutations in the DNA mismatch repair pathway. Hereditary nonpolyposis colorectal cancer (HNPCC also known as Lynch syndrome, is characterised by a risk of Colorectal cancer and other cancers of the endometrium BRCA1 and BRCA2, two famous mutations conferring a hugely increased risk of breast cancer on carriers, are both associated with a large number of DNA repair pathways, especially NHEJ and homologous recombination. BRCA1 ( Breast cancer 1 early onset is a Human Gene, some mutations of which are associated with a significant increase in the risk of Breast cancer BRCA2 (Breast Cancer Type 2 susceptibility protein is a Human Gene that is involved in the repair of chromosomal

Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Cells that are most rapidly dividing - most typically cancer cells - are preferentially affected. The side effect is that other non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected. Stem cells are cells found in most if not all multi-cellular Organisms. Modern cancer treatments attempt to localize the DNA damage to cells and tissues only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body).

DNA repair and evolution

The basic processes of DNA repair are highly conserved among both prokaryotes and eukaryotes and even among bacteriophage (viruses that infect bacteria); however, more complex organisms with more complex genomes have correspondingly more complex repair mechanisms. Conservation refers to a high degree of similarity in orthologous DNA sequences protein sequences, or Protein structures amongst various The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex This article is about a biological infectious particle for other uses see Phage (disambiguation. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have ^[33] The ability of a large number of protein structural motifs to catalyze relevant chemical reactions has played a significant role in the elaboration of repair mechanisms during evolution. In an unbranched chain-like biological Molecule, such as a Protein or a strand of RNA, a structural motif is a three-dimensional structural For an extremely detailed review of hypotheses relating to the evolution of DNA repair, see. ^[34]

The fossil record indicates that single celled life began to proliferate on the planet at some point during the Precambrian period, although exactly when recognizably modern life first emerged is unclear. FOSSIL is a standard protocol for allowing serial communication for Telecommunications programs under the DOS Operating system. The Precambrian ( Pre-Cambrian) is an informal name for the supereon comprising the eons of the Geologic timescale that came before the current Nucleic acids became the sole and universal means of encoding genetic information, requiring DNA repair mechanisms that in their basic form have been inherited by all extant life forms from their common ancestor. A nucleic acid is a Macromolecule composed of chains of monomeric Nucleotides In Biochemistry these Molecules carry Genetic information The emergence of Earth's oxygen-rich atmosphere (known as the "oxygen catastrophe") due to photosynthetic organisms, as well as the presence of potentially damaging free radicals in the cell due to oxidative phosphorylation, necessitated the evolution of DNA repair mechanisms that act specifically to counter the types of damage induced by oxidative stress. The Oxygen Catastrophe was a massive environmental change believed to have happened during the Siderian period at the beginning of the Paleoproterozoic Photosynthesis is a Metabolic pathway that converts Light Energy into Chemical energy. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell Oxidative phosphorylation is a Metabolic pathway that uses energy released by the oxidation of Nutrients to produce Adenosine triphosphate (ATP Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily

Rate of evolutionary change

On some occasions, DNA damage is not repaired, or is repaired by an error-prone mechanism which results in a change from the original sequence. When this occurs, mutations may propagate into the genomes of the cell's progeny. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism Should such an event occur in a germ line cell that will eventually produce a gamete, the mutation has the potential to be passed on to the organism's offspring. In Biology and Genetics, the germline of a mature or developing individual is the line (sequence of Germ cells that have genetic material that A gamete (from Ancient Greek γαμέτης; translated gamete = wife gametes = husband is a cell that fuses with another gamete The rate of evolution in a particular species (or, more narrowly, in a particular gene) is a function of the rate of mutation. eVolution is the third Album by eLDee, it was due to be released in 2008 Consequently, the rate and accuracy of DNA repair mechanisms have an influence over the process of evolutionary change. ^[35]

See also

References

External links

• DNA Repair - A summary of the primary mechanisms
• A comprehensive list of Human DNA Repair Genes
• 3D structures of some DNA repair enzymes
• Human DNA repair diseases
• DNA repair special interest group
• DNA Repair
• DNA Damage and DNA Repair
• Segmental Progeria