F08-BCH361-L15

F08-BCH361-L15 - DNA repair cancer and aging Proofing...

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DNA repair, cancer and aging
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Proofing •P r o o f i n g – on the average, DNA replication takes place only once each generation in each cell – errors in replication occur spontaneously only once in every 10 9 to 10 10 base pairs – errors in hydrogen bonding lead to errors in a growing DNA chain once in every 10 4 to 10 5 base pairs – DNA polymerase I uses its 3’ exonuclease activity to remove an incorrect nucleotide and add the correct one – existing DNA can also be repaired by DNA polymerase I using a cut-and-patch process called excision excision -repair repair
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The DNA polymerase I consists of two domains blue : polymerase-domain yellow 3’ 5’ exonuclease catalytic center of polymerase catalytic center of the 3’ 5’ exonuclease
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Why does the DNA contain thymine instead of uracil?
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DNA damage and repair
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Protection from cancer and ensured longevity are tightly linked in mammals. One of the fundamental mechanisms contributing to both is the cellular response toDNA damage.
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Main causes of DNA damage: A perplexing diversity of lesions arises in DNA from three main causes: Environmental agents such as the ultraviolet (UV) component of sunlight Ionizing radiation numerous genotoxic chemicals cause alterations in DNA structure
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mutation is predominantly cytotoxic or cytostatic (i.e. causes apoptosis or senescence, respectively, and thereby contributes to organismal ageing) A single DNA lesion can be characterised as mutation is predominantly mutagenic (i.e. causes mutations and thereby contributes to carcinogenesis) ∞∞∞∞ CANCER †††† Aging and cell death
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Mutagenic lessons Mutagenic lesions are typically small changes to the basepairing region of DNA bases , including: spontaneous deaminations depurinations oxidised bases. If left unrepaired, these lesions do not block DNA metabolic processes such as replication but can influence replication fidelity, thereby causing mutations and inevitably contributing to carcinogenesis. ∞∞∞∞ CANCER
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Cytotoxic lessons Cytotoxic lesions are a chemically diverse group of DNA lesions such as: double-strand breaks UV-induced bulky adducts DNA Iinterstrand crosslinks (ICLs) uncapped telomeres certain oxidised bases (e.g. thymine glycols and cyclopurines). Unrepaired cytotoxic lesions block vital DNA metabolic processes
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This note was uploaded on 09/30/2011 for the course BCH 361 taught by Professor Fromme during the Fall '08 term at ASU.

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F08-BCH361-L15 - DNA repair cancer and aging Proofing...

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