dna损伤与修复的分子基础课件.ppt

DNA损伤修复和基因突变培训课件.ppt

DNA损伤修复和基因突变,DNA损伤修复和基因突变,一自发性损伤,1.复制中的损伤复制中的损伤指复制过程中碱基配对时发生的误差再经过DNA聚合酶校读和单链结合蛋白等综合因素作用下仍然存在的DNA损伤.正常情况下,大肠杆菌复制过程中的错配率为,

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1、DNA damage and repair,Jun Mei(糜军),MD&Ph.DDepart.of Biochemistry and Molecular Cell Biology,Shanghai Jiao-Tong University School of Medicine,DNA damage and repairJun Mei(,DNA（脱氧核糖核酸）,Adenine Thymine Guanine Cytosine,1,2,3,4,5,+,糖苷键,戊糖,DNA（脱氧核糖核酸）Adenine,Base pair,氢键,Base pair氢键,Location of DNA,Nuclea

2、r DNA Chromatin/ChromosomeMitochondrial DNA Histone?,Location of DNANuclear DNA,The cause of DNA damageThe pattern of DNA damage,DNA damage,The cause of DNA damageDNA dam,The cause of DNA damage,Direct Radiation,UV,Chemical exposure Indirect Cellular metabolism,replication error,The cause of DNA dam

3、ageDirect,The pattern of DNA damage,OxidationAlkylation(methylation)HydrolysisBulky adduct formationMismatch,The pattern of DNA damageOxida,Direct cause of DNA damage,Pyrimidine dimer Oxidation,Direct cause of DNA damagePyri,Cytosine Methylated cytosine,Cytosine methylation,Cytosine Methyl,Indirect

4、cause of DNA damage,Indirect cause of DNA damage,Cellular response to DNA damage,Cellular response to DNA damag,DNA Repair,DNA Repair,Direct reversal repair,MGMT,methyl guanine methyl transferase,Direct reversal repairMGMT,me,Base excision repair,Base excision repair,Prokaryotes UvrA,UvrB,UvrC,DNA h

5、elicase IIEukaryotes XPA,XPB,XPC,XPD,XPE,XPF,XPG,CSA,CSB,ERCC1,RPA,Rad23 Transcription-coupled NER:CSA/CSB Global genomic NER:XPC/Rad23B,Nucleotide excision repair,ProkaryotesNucleotide excision,Mismatch repair,Mismatch repair,Double-strand Breaks Repair,Homologous Recombinant DSBA,SDSA,SSA,BIRNon-H

6、omologous End-joint,Double-strand Breaks RepairHom,Homologous Recombinant,Holliday Junction,Meiosis,DNA damage,Homologous RecombinantHolliday,SSA:Single strand annealingDSB occurred between two repeat sequencesResults in deletions of genetic material,BIR:Break-induced replicationDSB happened at the replication Forkmechanism is unclear,SSA:Single strand annealingBI,Enzymes involved HR,Enzymes involved HR,Non-Homologous End-joining,Non-Homologous End-joining,Determination of cellular response to D