分子生物学英文课件：DNA Damage and repair cuifuai.ppt

The TFIIH subunits of?XPD?and?XPB?act as a helicase and ATPase respectively 碱基错配修复（ mismatch repair） DNA mismatch repair?(MMR)?is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of?bases?that can arise during?DNA replication?and?recombination, as well as repairing some forms of?DNA damage. MutS , MutH and MutL Mismatch repair is strand-specific. In order to begin repair, the mismatch repair machinery distinguishes the newly synthesised strand from the template (parental). In gram-negative bacteria, transient hemimethylation?distinguishes the strands (the parental is?methylated ?and daughter is not). The parental GATC is?methylated MutH only cut the daughter strand Mismatch repair in E.coli MutS recognises the mismatched base on the daughter strand and binds the mutated DNA. MutH binds at hemimethylated sites along the daughter DNA, being activated by a MutL, which binds the MutS-DNA complex. MutH cuts the daughter strand in the hemimethylated site. The exonuclease digest the daughter strand from the cleavage site to beyond the mismatched site. DNA Polymerase III fill the single-strand gap . DNA ligase finally sealed. Dam methylase then rapidly methylates the daughter. MSH（MutS homologs） MLH and PMS (MutL homologs) In eukaryotes, newly synthesized lagging-strand DNA transiently contains nicks (before being sealed by DNA ligase) and provides a signal that directs mismatch proofreading systems to the appropriate strand. Mismatch repair in eukaryotes Homologous recombination repair Non homologous end jointing recombination repair Ⅲ Recombination repairing 同源重组修复 Recombination repairing in E.coli: rec A recB rec C 4. SOS repairing In bacteria, a coordinated induction of a variety of genes as a response to high levels of DNA damage. Less accurate, high mutation rate All genes, such as LexA, RecA, Uvr involving in SOS repairing, are composed of a regulon. Regulon: A group of genes or operons that are coordinatel