Inhibition of Msh6 ATPase Activity by Mispaired DNA Induces a Msh2(ATP)-Msh6(ATP) State Capable of Hydrolysis-Independent Movement along DNA

Dan J. Mazur, Marc L. Mendillo, Richard D. Kolodner*

*Corresponding author for this work

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

The Msh2-Msh6 heterodimer plays a key role in the repair of mispaired bases in DNA. Critical to its role in mismatch repair is the ATPase activity that resides within each subunit. Here we show that both subunits can simultaneously bind ATP and identify the Msh6 subunit as containing the high-affinity ATP binding site and Msh2 as containing a high-affinity ADP binding site. Stable binding of ATP to Msh6 causes decreased affinity of Msh2 for ADP, and binding to mispaired DNA stabilized the binding of ATP to Msh6. Our results support a model in which mispair binding encourages a dual-occupancy state with ATP bound to Msh6 and Msh2; this state supports hydrolysis-independent sliding along DNA.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalMolecular cell
Volume22
Issue number1
DOIs
StatePublished - Apr 7 2006

Keywords

  • CELLBIO
  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Inhibition of Msh6 ATPase Activity by Mispaired DNA Induces a Msh2(ATP)-Msh6(ATP) State Capable of Hydrolysis-Independent Movement along DNA'. Together they form a unique fingerprint.

  • Cite this