MCB7_8 - Common types of DNA damage! mistakes in DNA...

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Common types of DNA damage • mistakes in DNA synthesis • base hydrolysis, deamination, methylation, oxidation, or other damage • hydrolysis of the glycosidic or phosphodiester linkage • double-strand breaks • intrastrand or interstrand covalent cross-links such as pyrimidine dimers UV light (in sunshine) readily induces intrastrand pyrimidine dimers, usually the thymine dimer shown below: 1
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Spontaneous wear and tear creates damaged DNA an abasic site These are common examples of spontaneous DNA damage uracil in DNA Deamination of an intentionally 5meC, common in eukaryotes like us, gives rise to another normal base, T. Does T get repaired or stay mispaired with G? 2
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Different types of repair mechanism correct different types of DNA damage In increasing order of the complexity of the problem: • direct repair of a specific base modification • base excision repair when one base is missing or altered • (oligo)nucleotide excision repair when there is a distortion of B-form DNA with damage on one strand • mismatch repair when both bases are OK but their paired combination is not • error-prone repair of damage to one strand when the other is not present to provide a template • repair of a double-stranded DNA break 3
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This is not wise as a general repair mechanism, because new or unusual types of damage will not be possible to repair. But, it can increase the efficiency of correcting common damage. For example, E. coli has a specific enzyme to remove the methyl group from O 6 -methylguanine, directly reversing the modification. However, the enzyme commits ‘suicide’ by self-modification and must then be degraded.
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MCB7_8 - Common types of DNA damage! mistakes in DNA...

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