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The most common causes of death are skin cancer

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Unformatted text preview: nt). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years). ADP + Pi h p://www.ncbi.nlm.nih.gov/books/NBK1397/ 9 Alkylating agents include: • nitrogen mustard • ethylnitrosourea • MNNG O6-methylguanine base pairs with either T or C 10 Chemical mutagens: oxidizers Chemical mutagens: alkylating agents A common alkylation product: Hereditary nonpolyposis colorectal cancer syndrome mutations present in 1 in 200 in the US population. >100 di erent oxidative DNA modi cations This and other O6-alkylguanine adducts can be removed by MGMT, a one-shot direct repair protein* that transfers the alkyl moiety to an active site Cys residue. *Not an enzyme! The protein can be used only once, and is then degraded. Note that other powerful oxidizers are produced through normal metabolism! 11 12 Base excision repair Uracil-DNA Glycosylase* catalyzes base excision 1....
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