9.dna损伤与修复的分子基础38.pptVIP

Physiological regulation of DNA repair Key factors: Nutrition Aging Neuroendocrine (Sleeping) …… Recommended Reading ATM and Related Protein Kinases: Safeguard Genome Integrity. Nature Reviews Cancer 2003;3;155-168 Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nature reviews Molecular Cell Biology 2008;9:759-769 DNA-PK The means to justify the Ends. Advances in Immunology 2008;99:33-58 ATR: an essential regulator of genome integrity. Nature reviews Molecular Cell Biology 2008;9:616-627 离子键、共价键、氢键 * * Mitochondrial DNA and nuclear DNA * Thymine dimers, pyrimidine dimers, cyclobutane pyrimidine dimers (CPD), UV-endonuclease-sensitive-sites (ESS). * Bap，苯并芘；BPDE，二羟环氧苯并芘；Acrolein，丙烯醛。 * A. Direct repair, also named with Direct reversal β-sliding clamp/PCNA DSBR: double-strand break repair; SDSA: synthesis-dependent strand annealing. * * 9-1-1 complex containing Rad9, Rad1, Rad17, Hus1 proteins. * 这里是一个举例说明，DNA损伤后怎样通过ATM、ATR调节细胞周期。我们可以看到DNA损伤后，ATM、ATR对处于各种不同周期的细胞都有调节作用。 * ATM: ataxia-telangiectasia mutant; ATR: ATM and RAD3-related * DNA damage and repair Jun Mei (糜军), MD Ph.D Depart. of Biochemistry and Molecular Cell Biology, Shanghai Jiao-Tong University School of Medicine DNA（脱氧核糖核酸） Adenine Thymine Guanine Cytosine 1 2 3 4 5 + 糖苷键 戊糖 Base pair 氢键 Location of DNA Nuclear DNA Chromatin/Chromosome Mitochondrial DNA Histone? The cause of DNA damage The pattern of DNA damage DNA damage The cause of DNA damage Direct Radiation, UV, Chemical exposure Indirect Cellular metabolism, replication error The pattern of DNA damage Oxidation Alkylation (methylation) Hydrolysis Bulky adduct formation Mismatch Direct cause of DNA damage Pyrimidine dimer Oxidation Cytosine Methylated cytosine Cytosine methylation Indirect cause of DNA damage Cellular response to DNA damage DNA Repair Direct reversal repair MGMT, methyl guanine methyl tran