生化2014c15dnadamageandrepair精品课件.pptVIP

Main Contents Direct repair of pyrimidine dimer * Direct repair of alkylated base * Direct repair of depurination site Rebuild of glycosyl bond catalyzed by DNA purine insertion enzyme,leading to the purine direct insertion, which has very high specificity Direct repair of single strand breakage Rebuild of phosphodiester bond by DNA ligase * 2. Excision repair of DNA damage Base excision repair Nucleotide excision repair * Base excision repair ① to recognize and to hydrolyze：the impaired base is recognized and hydrolyzed by DNA glycosylase specifically, leading to the abasic site ② to cut off：the phosphodiester bond at 5’-end of the depurination site is cut off, releasing the ribose phosphate ③ to synthesize：the complementary sequence is repaired on the gap by DNA polymerase using the opposite strand as template ④ linkage：by DNA ligase, DNA structure return normal * * Nucleotide excision repair ① First, the impaired DNA fragment is recognized by one enzyme system; ② Second, the impaired DNA fragment is cut off from its two sides; ③ Third, the complementary sequence is synthesized by DNA polymerase, using another strand as template; ④ Finally, the gap is linked by DNA ligase, the impaired DNA is repaired completely. * NER in E.coli is consist of 4 kinds of protein UvrA UvrB UvrC UvrD * Nucleotide excision repair of human DNA damage ① The impaired fragment is recognized by XPC,XPA, SSB binding to the impaired site of DNA; ② XPB,XPD play the role of helicase, leading to form a bulge around the impaired DNA; ③ Comformation of XPG XPF is changed,exerting the endonuclase activity to cut the impaired fragment at 3’-end and 5’-end and release it, with the help of PCNA; ④ The remaining deletion region is repaired by polymerase δor ε; ⑤ Finally,it is linked by DNA ligase * Not only NER repair the entire genome of damage DNA, but also rescue the RNA polymerase which has stopped work due to transcript template damage, called transcription-coupled repair Mode of action: