Identification of Exo1-Msh2 interaction motifs in DNA mismatch repair and new Msh2-binding partners

Eva M. Goellner, Christopher D. Putnam, William J. Graham, Christine M. Rahal, Bin Zhong Li, Richard D. Kolodner

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Eukaryotic DNA mismatch repair (MMR) involves both exonuclease 1 (Exo1)-dependent and Exo1-independent pathways. We found that the unstructured C-terminal domain of Saccharomyces cerevisiae Exo1 contains two MutS homolog 2 (Msh2)-interacting peptide (SHIP) boxes downstream from the MutL homolog 1 (Mlh1)-interacting peptide (MIP) box. These three sites were redundant in Exo1-dependent MMR in vivo and could be replaced by a fusion protein between an N-terminal fragment of Exo1 and Msh6. The SHIP-Msh2 interactions were eliminated by the msh2M470I mutation, and wild-type but not mutant SHIP peptides eliminated Exo1-dependent MMR in vitro. We identified two S. cerevisiae SHIP-box-containing proteins and three candidate human SHIP-box-containing proteins. One of these, Fun30, had a small role in Exo1-dependent MMR in vivo. The Remodeling of the Structure of Chromatin (Rsc) complex also functioned in both Exo1-dependent and Exo1-independent MMR in vivo. Our results identified two modes of Exo1 recruitment and a peptide module that mediates interactions between Msh2 and other proteins, and they support a model in which Exo1 functions in MMR by being tethered to the Msh2–Msh6 complex.

Original languageEnglish
Pages (from-to)650-659
Number of pages10
JournalNature Structural and Molecular Biology
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2018

Bibliographical note

Publisher Copyright:
© 2018, The Author(s).

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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