Types of dna damage and repair pdf

Dna lesions can occur in many different forms, including apurinicapyrimidinic ap sites abasic sites, adducts, singlestrand breaks ssbs, dsbs, dnaprotein crosslinks, and insertiondeletion mismatches. Apr 17, 2016 difference between dna damage and mutation dna damage dna mutation physical abnormalities in the dna is a change in the base sequence of the dna can be recognized by enzymes cannot be recognized by enzymes once the base change is present in both dna strands can be correctly repaired if redundant information, such as the. Mechanisms of dna damage, repair, and mutagenesis article pdf available in environmental and molecular mutagenesis 581 may 2017 with 7,565 reads how we measure reads. Then fills in with pol on 3oends, and attaches 5o end with ligase. Included in the table are components of the pathways for nucleotide excision repair, mismatch repair, dna damage checkpoint, nonhomologous end joining, homologous. Dna damage and inaccurate repair mechanisms jointly cause. Dna damage and dna repair spontaneous loss of bases alkylation of bases oxidation of bases uvlight induced damage.

In this post, we will just mention the names of different dna repair mechanisms. Dna damage sensors recognize damage or aberrations to the genomic sequence, which can then activate signal transducers to signal the appropriate repair pathways effectors zhou and elledge, 2000. Consequently, the various types of excision repair are the most important dna repair mechanisms in both prokaryotic and eukaryotic cells. Dna repair california state university, northridge. Dna damage can be categorized into two main classes based on its origin. Damage to dna, including oxidative dna damage, has been implicated in the development of a variety of cancers including colon, breast and prostate. Major dna repair pathways are mismatch repair mmr, nucleotide excision repair ner, base excision repair ber, homologous recombinational. The precr repair mix can be used in conjunction with any thermophilic polymerase. So far there are six different types of dna repair mechanisms known to science.

Mechanisms of dna damage, repair and mutagenesis ncbi. Among the known dna repair processes in humans, one typenucleotide excision repair nerspecifically protects against mutations caused. The repair of uracil containing dna is a good example of baseexcision repair, in which single damaged bases are recognized and removed from the dna molecule figure 5. When watson and crick described the double helix structure of dna and proposed its semiconservative replication based on specific base pairings to explain the faithful transmission of genetic information from generation to generation mechanism to explain spontaneous mutations watson and crick pointed out that the structures of the bases in dna are not static. Natural cellular processes, exposure to radiation cosmic, medical e. Multiple cell types show persistent dna damage and a range of lesions. Many of these dna damage response genes are conserved from mammals to yeast zhou and elledge, 2000. In human cells, both normal metabolic activities and environmental factors such as radiation can cause dna damage, resulting in as many as 1 million individual molecular lesions per cell per day. A deficiency in dna repair would cause more dna damage to accumulate, and increase the risk for cancer. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division.

Although direct repair is an efficient way of dealing with particular types of dna damage, excision repair is a more general means of repairing a wide variety of chemical alterations to dna. It is now in widespread use in genetic toxicology and oncology. The central role of dna damage in progression to cancer is indicated at the second level of the figure. The central elements of dna damage, epigenetic alterations and deficient dna repair in progression to cancer are shown in red. Dna is repaired by several different mechanisms besides proofreading by replication enzymes dna polymerases can remove an incorrect nucleotide immediately after its addition to the growing end of the chain. Oxidative dna damage refers to the oxidation of specific bases. Genomic and molecular landscape of dna damage repair. Numerous proteins and pathways have been involved in these processes. Three types of excision repairbaseexcision repair, nucleotideexcision repair, and mismatch repairenable cells to cope with a variety of different kinds of dna damage. Dna replication skips over a lesion and requires homologous recombination mediated by the reca protein after replication sos repair in e.

Xrays, radiation therapy and some forms of chemotherapy. Dna repair is a collection of processes by which a cell identifies and corrects damage to the dna molecules that encode its genome. Major dna repair pathways are mismatch repair mmr, nucleotide excision repair ner, base excision repair ber, homologous recombinational repair hr, and nonhomologous end joining nhej. One of the most frequent is the loss of an amino group deamination resulting, for example, in a c being converted to a u. Common causes of such dna damage include ultraviolet uv light, which induces the formation of cyclobutane pyrimidinepyrimidine dimers, and smoking, which causes formation of benzo apyreneguanine adducts. Dsbr is another repair mechanism for damaged dna by homologous and non homologous end joining. Table 1 is a summary of some dna damage response genes identified in the c.

Formation of pyrimidine dimers thymine dimers and 6. The endogenous damages are the damage caused by reactive oxygen species or some agents else produced from normal metabolic byproducts, while exogenous damages are caused by external agents, like some radiations, include uv, xrays. Endogenous and exogenous damage are breaks in the dna strands which are caused by ionizing radiation created by radioactive decay or in cosmic rays and these dna damages can be induced by lowlevel ionizing radiation and can lead to replicational and transcriptional errors muthusamy, 20. In the meiotic region of the germ line, cells with dna damage are removed by apoptosis before oogenesis. Deficiencies in dna repair in humans can lead to conditions, such as xeroderma pigmentosum. As dna damage occurs within the chromatin, we postulate that modifications of histones are important for signaling the position of dna damage, recruiting the dna repair proteins to the site of damage, and creating an open structure such that the repair proteins can access the site of damage. This could result in the development of a variety of cancers including colon, breast, and prostate. Dna damage is an inevitable consequence of using water in the cytoplasm, breathing air, eating food, and being exposed to sunlight and cosmic rays. Cells have active mechanisms to repair the damage, and defective repair mechanisms can lead to profound developmental problems as well as greatly increased cancer susceptibility.

Pdf mechanisms of dna damage, repair, and mutagenesis. This dna damage and repair lecture explains the dna damage response created by p53 and other dna damage sensitive proteins to repair dna structure and prevent mutation. Here we discuss the various types of damage to dna, including oxidative damage, hydrolytic damage, dna strand breaks, and others. The molecular mechanism of dna repair mechanisms in the cells and different types of dna structural lesions and its causes ppt and pdf. Excision repair is one of the types of dna repair systems, which is an enzymatic process and follows a cut, copy and paste mechanism. In human cells, both normal metabolic activities and. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Xrays, radiation therapy and some forms of chemotherapy commonly occurring types of dna damage. Since the sources of dna damage can be roughly divided into two main groups, endogenous damage and exogenous damage. There are different types of dna damage and therefore different molecular pathways of dna repair to correct them, including nonhomologous end joining, homologous recombination, mismatch repair and nucleotide excision repair. Dna repair pathways direct enzymatic repair base excision repair nucleotide excision repair mismatch repair doublestrand break repair nonhomologous end joining homologous recombination. The dna damage and precr table lists some possible dna samples and the impact of the damage they may undergo. Sep 18, 2017 dna repair is a collection of processes by which a cell identifies and corrects damage to the dna molecules that encode its genome.

Dandrea 1, 2, 3, 6 abstract dnadamaging agents are widely used in clinical oncology and exploit defi ciencies. Dna damage affecting both genomic and mitochondrial dna is present in a variety of both inherited and acquired vascular diseases. In turn, dna damage activates a variety of dna repair mechanisms, many of which are activated in vascular disease. Such dna repair mechanisms either stall the cell cycle to allow repair to occur. This type of system can repair many types of dna damage. Learn vocabulary, terms, and more with flashcards, games, and other study tools.

Dna damage induced apoptosis occurs in addition to physiological programmed germ cell death. Recently oxidative rna damage has been described in conjunction with a wide variety of neurological diseases including alzheimers. Naturally occurring oxidative dna damages arise at. Excision repair it is a general repair system that corrects damage which causes distortions in. Novel types of dnasugar damage in neocarzinostatin cytotoxicity and mutagenesis. Damage to dna that occurs naturally can result from metabolic or hydrolytic processes. Each repair pathway is directed to specific types of damage, and a given type of damage can be targeted by several pathways. An important general process for dna repair is nucleotide excision repair ner. Dna double strand breaks dsb are the most toxic form of dna damage. Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. Endogenous and environmental agents can cause dna damage in cells 1, 10, 18.

The dna damage in germ cell is of three main types viz. Dna damage, especially doublestrand breaks dsbs, due to exogenous e. Different types of repair fix different types of damage in increasing order of complexity of the problem. Mutations to checkpoint kinases can ultimately lead to decreased dna repair and increased susceptibility to cancer. All four of the bases in dna a, t, c, g can be covalently modified at various positions one of the most frequent is the loss of an amino group deamination resulting, for example, in a c being converted to a u. The different types of dna repair include direct repair, base excision repair, nucleotide excision repair ner, doublestrand break repair including homologous recombination and nonhomologous end joining, and crosslink repair sancar et al. Base excision repair ber, nucleotide excision repair ner, and the direct damage reversalrepair dr pathways repair dna base damage, while mismatch repair mmr corrects base mispairs and small loops often found in repetitive sequence dna. It is related with programmed dna breaks in lymphoid cells.

Dna damage and repair biomarkers of immunotherapy response kent w. Different types of repair fix different types of damage. A cutting mechanism involves, removal of the damaged part or unusual bases by the specific enzymes like glycosylases and helicases. Eukaryotic cells can repair many types of dna damage. Cells have evolved efficient mechanisms to repair dna damage and thereby prevent chromosomal. Types of dna damage all four of the bases in dna a, t, c, g can be covalently modified at various positions. The consequences of a type of lesion depend on three things, something like. The scientists found that different types of dna alterations induced by the same genotoxin are often fixed by different dna repair pathways, some errorfree, others errorprone. Rauchman, in translating epigenetics to the clinic, 2017. Miscoding lesions and other types of damage can kill or dysregulate the cell.

Many modifications, like 6methyla, are normal, not miscoding. Dna is susceptible to many types of damage resulting from exposure to a variety of chemical or environmental agents, manipulation or simply aging. Mar 11, 2015 this dna damage and repair lecture explains the dna damage response created by p53 and other dna damage sensitive proteins to repair dna structure and prevent mutation. When watson and crick described the double helix structure of dna and proposed its semiconservative replication based on specific base pairings to explain the faithful transmission of genetic information from generation to generation mechanism to explain spontaneous mutations. Cyclobutane dimers 6,4,photoproducts dna strand breaks. Let us make an indepth study of the dna damage types and repair mechanisms. It became apparent that dna in all living organisms continually incurs a myriad of types of damage, and that cells have devised ingenious. Many of these lesions cause structural damage to the dna molecule. The pathway of cellular dna damage and repair that leads to senescence, apoptosis, or cancer to compensate for the degree and types of dna damage that occur, cells have developed multiple repair processes including mismatch, base excision, and nucleotide excision repair mechanisms, with little process redundancy. Difference between dna damage and mutation dna damage dna mutation physical abnormalities in the dna is a change in the base sequence of the dna can be recognized by enzymes cannot be recognized by enzymes once the base change is present in both dna strands can be correctly repaired if redundant information, such as the. Metabolism releases compounds that damage dna including reactive oxygen species, reactive nitrogen species, reactive carbonyl species, lipid peroxidation products and alkylating agents, among others, while hydrolysis cleaves chemical bonds in dna.