2020 journal article

Dynamic human MutS alpha-MutL alpha complexes compact mismatched DNA

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 117(28), 16302–16312.

By: K. Bradford*, H. Wilkins*, P. Hao n, Z. Li*, B. Wang*, D. Burke*, D. Wu*, A. Smith* ...

author keywords: DNA repair; AFM; MutS; MutL; DREEM
MeSH headings : Adenosine Triphosphate / metabolism; DNA / chemistry; DNA / genetics; DNA / metabolism; DNA Mismatch Repair; DNA-Binding Proteins / chemistry; DNA-Binding Proteins / metabolism; Humans; Multiprotein Complexes / metabolism; MutL Proteins / chemistry; MutL Proteins / metabolism; MutS Homolog 2 Protein / chemistry; MutS Homolog 2 Protein / metabolism; Nucleic Acid Conformation; Nucleosomes / metabolism; Protein Folding; Protein Multimerization
Source: Web Of Science
Added: August 17, 2020

Significance Mismatch repair is the process that corrects replication errors. Mutations in the proteins MutSα and MutLα that initiate MMR are responsible for Lynch syndrome, the most common hereditary cancer. We present results showing surprising stoichiometries and conformations of human MutSα and MutLα mismatch repair initiation complexes. Moreover, these multimeric MutSα–MutLα complexes reconfigure the DNA in the vicinity of the mismatch. These complexes may not only mark the position of the mismatch but also could protect it from nucleosome reloading and potentially remodel adjacent nucleosomes. These results contrast with current models in the field, which envision mobile 1:1 MutSα–MutLα complexes that leave the mismatch. Our results provide a framework for thinking about MMR initiation.