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
• 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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- Spring '14
- DNA, DNA repair, DNA Damage