Differential mismatch recognition specificities of eukaryotic MutS homologs, MutS? and MutS?.

ABSTRACT: In eukaryotes, the recognition of the DNA postreplication errors and initiation of the mismatch repair is carried out by two MutS homologs: MutS? and MutS?. MutS? recognizes base mismatches and 1 to 2 unpaired nucleotides whereas MutS? recognizes longer insertion-deletion loops (IDLs) with 1 to 15 unpaired nucleotides as well as certain mismatches. Results from molecular dynamics simulations of native MutS?:IDL-containing DNA and MutS?:mismatch DNA complexes as well as complexes with swapped DNA substrates provide mechanistic insight into how the differential substrate specificities are achieved by MutS? and MutS?, respectively. Our simulations results suggest more extensive interactions between MutS? and IDL-DNA and between MutS? and mismatch-containing DNA that suggest corresponding differences in stability. Furthermore, our simulations suggest more expanded mechanistic details involving a different degree of bending when DNA is bound to either MutS? or MutS? and a more likely opening of the clamp domains when noncognate substrates are bound. The simulation results also provide detailed information on key residues in MutS? and MutS? that are likely involved in recognizing IDL-DNA and mismatch-containing DNA, respectively.

SUBMITTER: Sharma M 

PROVIDER: S-EPMC4052273 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature