The N terminus of Saccharomyces cerevisiae Msh6 is an unstructured tether to PCNA

Mol Cell. 2007 May 25;26(4):565-78. doi: 10.1016/j.molcel.2007.04.024.

Abstract

The eukaryotic MutS homolog complexes, Msh2-Msh6 and Msh2-Msh3, recognize mismatched bases in DNA during mismatch repair (MMR). The eukaryote-specific N-terminal regions (NTRs) of Msh6 and Msh3 have not been characterized other than by demonstrating that they contain an N-terminal PCNA-interacting motif. Here we have demonstrated genetically that the NTR of Msh6 has an important role in MMR that is partially redundant with PCNA binding. Small-angle X-ray scattering (SAXS) was used to determine the solution structure of the complex of PCNA with Msh2-Msh6 and with the isolated Msh6 NTR, revealing that the Msh6 NTR is a natively disordered domain that forms an extended tether between Msh6 and PCNA. Moreover, computational analysis of PCNA-interacting motifs in the S. cerevisiae proteome indicated that flexible linkers are a common theme for PCNA-interacting proteins that may serve to localize these binding partners without tightly restraining them to the immediate vicinity of PCNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pair Mismatch
  • Chromatography, Gel
  • DNA, Fungal / genetics
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Genetic Complementation Test
  • Mass Spectrometry
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Plasmids
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Deletion

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • MSH6 protein, S cerevisiae
  • Peptide Fragments
  • Proliferating Cell Nuclear Antigen
  • Saccharomyces cerevisiae Proteins