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 journalArticle

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 1 2013
Externally publishedYes

Fingerprint

Endonucleases
Hydrolysis
Adenosine Triphosphate
DNA Mismatch Repair
Repair
DNA
Adenosine Triphosphatases
Chemical activation
Degradation
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Shimada, A., Kawasoe, Y., Hata, Y., Takahashi, T. S., Masui, R., Kuramitsu, S., & Fukui, K. (2013). MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner. FEBS Journal, 280(14), 3467-3479. https://doi.org/10.1111/febs.12344

MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner. / Shimada, Atsuhiro; Kawasoe, Yoshitaka; Hata, Yoshito; Takahashi, Tatsuro S.; Masui, Ryoji; Kuramitsu, Seiki; Fukui, Kenji.

In: FEBS Journal, Vol. 280, No. 14, 01.07.2013, p. 3467-3479.

Research output: Contribution to journalArticle

Shimada, A, Kawasoe, Y, Hata, Y, Takahashi, TS, Masui, R, Kuramitsu, S & Fukui, K 2013, 'MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner', FEBS Journal, vol. 280, no. 14, pp. 3467-3479. https://doi.org/10.1111/febs.12344
Shimada, Atsuhiro ; Kawasoe, Yoshitaka ; Hata, Yoshito ; Takahashi, Tatsuro S. ; Masui, Ryoji ; Kuramitsu, Seiki ; Fukui, Kenji. / MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner. In: FEBS Journal. 2013 ; Vol. 280, No. 14. pp. 3467-3479.
@article{b3f3c58a1aa843e5a59db829aaec0b84,
title = "MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner",
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.",
author = "Atsuhiro Shimada and Yoshitaka Kawasoe and Yoshito Hata and Takahashi, {Tatsuro S.} and Ryoji Masui and Seiki Kuramitsu and Kenji Fukui",
year = "2013",
month = "7",
day = "1",
doi = "10.1111/febs.12344",
language = "English",
volume = "280",
pages = "3467--3479",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "14",

}

TY - JOUR

T1 - MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner

AU - Shimada, Atsuhiro

AU - Kawasoe, Yoshitaka

AU - Hata, Yoshito

AU - Takahashi, Tatsuro S.

AU - Masui, Ryoji

AU - Kuramitsu, Seiki

AU - Fukui, Kenji

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84879894111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879894111&partnerID=8YFLogxK

U2 - 10.1111/febs.12344

DO - 10.1111/febs.12344

M3 - Article

C2 - 23679952

AN - SCOPUS:84879894111

VL - 280

SP - 3467

EP - 3479

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 14

ER -