MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner

Atsuhiro Shimada, Yoshitaka Kawasoe, Yoshito Hata, Tatsuro S. Takahashi, Ryoji Masui, Seiki Kuramitsu, Kenji Fukui

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

In the initial steps of DNA mismatch repair, MutS recognizes a mismatched base and recruits the latent endonuclease MutL onto the mismatch-containing DNA in concert with other proteins. MutL then cleaves the error-containing strand to introduce an entry point for the downstream excision reaction. Because MutL has no intrinsic ability to recognize a mismatch and discriminate between newly synthesized and template strands, the endonuclease activity of MutL is strictly regulated by ATP-binding in order to avoid nonspecific degradation of the genomic DNA. However, the activation mechanism for its endonuclease activity remains unclear. In this study, we found that the coexistence of a mismatch, ATP and MutS unlocks the ATP-binding-dependent suppression of MutL endonuclease activity. Interestingly, ATPase-deficient mutants of MutS were unable to activate MutL. Furthermore, wild-type MutS activated ATPase-deficient mutants of MutL less efficiently than wild-type MutL. We concluded that ATP hydrolysis by MutS and MutL is involved in the mismatch-dependent activation of MutL endonuclease activity. MutS and MutL participate in the initial steps in DNA mismatch repair. The role of their ATP hydrolysis in the repair pathway has been barely understood.

Original languageEnglish
Pages (from-to)3467-3479
Number of pages13
JournalFEBS Journal
Volume280
Issue number14
DOIs
Publication statusPublished - Jul 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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