DNA Mismatch Repair (original) (raw)

The Scripps Research Institute been established in E. coli. MMR is initiated when MutS recognizes and binds to mis-La Jolla, California † Cell and Molecular Biology matched DNA. Prokaryotic MutS forms homodimers that can recognize a variety of DNA substrates, including mispairs and Life Sciences Division Lawrence Berkeley National Laboratory small insertion/deletion loops. Eukaryotic MutS homologs (MSHs) form different heterodimers that can recognize different Berkeley, California DNA substrates, including not only mispairs and loops, but also single-strand flaps, Holliday junctions and various chemical lesions [3, 11]. MSHs contain nucleotide binding Walker A and Summary B motifs and extensive research was aimed at determining the role of ATP in MutS function and MMR. A defining observation DNA mismatch repair (MMR) is initiated when the MutS prowas that MSH2/6 binds to damaged DNA in the ADP-bound tein recognizes damaged DNA. Crystal structures of MutS state and that binding to mismatched DNA stimulates ATP bound to mispaired and unpaired DNA show how MutS distinbinding and hydrolysis [12]. Furthermore, ATP binding induces guishes damaged from undamaged DNA and explain how a a conformational change in MSH2/6, which can diffuse along broad variety of DNA mismatch lesions can be detected. the DNA [13] and was suggested to form a sliding clamp and The structures suggest mechanisms for the ATP-induced to promote ␣-loop formation [14, 15]. However, the role of ATP structural regulation of multistep DNA repair processes.