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DNA damage response reaction

DNA damage response reaction. Annu . Rev. Biochem . 2004. 73:39-85 . DNA Base damages. Cisplatin , mitomycin C, psoralen , nitrogen mustard, and adriamycin. Annu . Rev. Biochem . 2004. 73 :39-85 . DNA Backbone damages. Cisplatin , mitomycin D,

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DNA damage response reaction

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  1. DNA damage response reaction Annu. Rev. Biochem. 2004. 73:39-85

  2. DNA Base damages Cisplatin, mitomycin C, psoralen, nitrogen mustard, and adriamycin Annu. Rev. Biochem. 2004. 73:39-85

  3. DNA Backbone damages Cisplatin, mitomycin D, psoralen, nitrogen mustard, Ionizing radiation Base excision repair/ NER Annu. Rev. Biochem. 2004. 73:39-85

  4. Learn from photolyase UV An induced fit mechanism: For efficient electron transfer, the flavin and the pyrimidine dimer need to be in direct contact ♦ backbone recognition ♦ dinucleotide recognition ♦ Electron transfer cannot occur to normal bases Annu. Rev. Biochem. 2004. 73:39-85

  5. Replication fork arrest DNA damage Replication fork arrest Replication fork arrest ATM ATR Checkpoint arrest, DNA repair and apoptosis Genomic instability Cancer/ neurodegenerative disease

  6. Ataxia Telangiectasia multifaceted phenotype (1926) “6.6% of all breast cancers in the US may occur in A-T heterozygous women” “Up to sevenfold increase of cancer risk Among A-T carriers” “Many abnormalities may be the outcome of a state of continuous stress caused by the basic defect” Annu. Rev. Genet. 1997. 31:635-662

  7. Localization of an A-T gene to Chr 11q22-23 Nature336, 577-580 (1988)

  8. Physical Mapping “A putative protein that is similar to several yeast and mammalian phosphatidylinosito-3’ kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control” Science 268, 1749-1753 (1995)

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