Prerecognition Diffusion Mechanism of Human DNA Mismatch Repair Proteins along DNA: Msh2-Msh3 versus Msh2-Msh6.

ABSTRACT: DNA mismatch repair (MMR) is an important postreplication process that eliminates mispaired or unpaired nucleotides to ensure genomic replication fidelity. In humans, Msh2-Msh6 and Msh2-Msh3 are the two mismatch repair initiation factors that recognize DNA lesions. While X-ray crystal structures exist for these proteins in complex with DNA lesions, little is known about their structures during the initial search along nonspecific double-stranded DNA, because they are short-lived and difficult to determine experimentally. In this study, various computational approaches were used to sidestep these difficulties. All-atom and coarse-grained simulations based on the crystal structures of Msh2-Msh3 and Msh2-Msh6 showed no translation along the DNA, suggesting that the initial search conformation

SUBMITTER: Pal A 

PROVIDER: S-EPMC7872316 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature