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

27 Scopus citations


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
Issue number8
StatePublished - Aug 1 2018

Bibliographical note

Funding Information:
We would like to thank N. Bowen for helpful discussions and for providing many of the different protein preparations used in the in vitro MMR assays. This work was supported by NIH grants K99 ES026653 (E.M.G.), F32 CA210407 (W.J.G.) and R01 GM50006 (R.D.K.) and by the Ludwig Institute for Cancer Research (R.D.K. and C.D.P.).

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

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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