文档介绍：DNA REPAIR
BASE EXCISION REPAIR
NUCLEOTIED EXCISION REPAIR
MISMATCH REPAIR
STRAND BREAK REPAIR
DNA Repair
Mutations are rare events,
1 per 109-1010 base pairs per cell division.
misincorporation during DNA synthesis yields plementary base pairs or mismatches
Mutations can also arise via incorporation of chemically damaged nucleotides or by incorporation of an undamaged nucleotide opposite a damaged base within the template strand.
Strand slippage or formation of unusual secondary structures within DNA, especially within repetitive sequences, can also result in mutations when processed aberrantly during replication, bination, or repair.
MisMatch Repair
Ravi R. Iyer, Anna Pluciennik, Vickers Burdett, and Paul L. Modrich, DNA Mismatch Repair: Functions and Mechanisms Chem. Rev. 2006, 106, 302-323.
Thomas Jascur* and C. Richard Boland, Structure and function of ponents of the human DNA mismatch repair system Int. J. Cancer: 119, 2030–2035 (2006)
MisMatch Repair
ic inactivation of the mismatch repair system elevates spontaneous mutability 50-1000-fold.
Mismatch repair defects lead to highly elevated rates of base substitution and frameshift mutations, permit illegitimate bination between quasi-homologous sequences, and render mammalian cells resistant to the cytotoxic effects of several classes of DNA damaging agents.
Inactivation of the human mismatch repair system is the cause of hereditary nonpolyposis colon cancer ()and has been implicated in the development of a subset of sporadic tumors that occur in a variety of tissues.
Mismatch repair
MMR system is an excision/resynthesis system that can be divided into 4 phases:
(i) recognition of a mismatch by MutS proteins,
(ii) recruitment of repair enzymes
(iii) excision of the incorrect sequence,
(iv) resynthesis by DNA polymerase using the parental strand as a template.
Mismatch Repair in
MutS is responsible for initiation of E. coli mismatch repair.
95 kDa polypeptide, which exists as an equil