1、Adenine Thymine Guanine Cytosine12345+糖苷键糖苷键戊糖戊糖氢键氢键Nuclear DNA Chromatin/ChromosomeMitochondrial DNA Histone?The cause of DNA damage The pattern of DNA damage Direct Radiation,UV,Chemical exposure Indirect Cellular metabolism,replication error Oxidation Alkylation(methylation)Hydrolysis Bulky adduc
2、t formation MismatchPyrimidine dimer OxidationCytosine Methylated cytosineMGMT,methyl guanine methyl transferaseProkaryotes UvrA,UvrB,UvrC,DNA helicase IIEukaryotes XPA,XPB,XPC,XPD,XPE,XPF,XPG,CSA,CSB,ERCC1,RPA,Rad23 Transcription-coupled NER:CSA/CSB Global genomic NER:XPC/Rad23BHomologous Recombina
3、nt DSBA,SDSA,SSA,BIRNon-Homologous End-jointHolliday JunctionMeiosisDNA damageSSA:Single strand annealingDSB occurred between two repeat sequencesResults in deletions of genetic materialBIR:Break-induced replicationDSB happened at the replication Forkmechanism is unclear(9-1-1 complex)ATM,ATR,DNA-PK
4、Cell cycle regulation in Response to DNA damagePIP2PIP3PI3KPTENINPP4BAktKey factors:NutritionAgingNeuroendocrine(Sleeping)ATM and Related Protein Kinases:Safeguard Genome Integrity.Nature Reviews Cancer 2003;3;155-168Ataxia-telangiectasia:from a rare disorder to a paradigm for cell signalling and cancer.Nature reviews Molecular Cell Biology 2008;9:759-769DNA-PK The means to justify the Ends.Advances in Immunology 2008;99:33-58ATR:an essential regulator of genome integrity.Nature reviews Molecular Cell Biology 2008;9:616-627
