Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA - PubMed (original) (raw)

Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA

Dan J Mazur et al. Mol Cell. 2006.

Free article

Abstract

The Msh2-Msh6 heterodimer plays a key role in the repair of mispaired bases in DNA. Critical to its role in mismatch repair is the ATPase activity that resides within each subunit. Here we show that both subunits can simultaneously bind ATP and identify the Msh6 subunit as containing the high-affinity ATP binding site and Msh2 as containing a high-affinity ADP binding site. Stable binding of ATP to Msh6 causes decreased affinity of Msh2 for ADP, and binding to mispaired DNA stabilized the binding of ATP to Msh6. Our results support a model in which mispair binding encourages a dual-occupancy state with ATP bound to Msh6 and Msh2; this state supports hydrolysis-independent sliding along DNA.

PubMed Disclaimer

Cited by

Mismatch Repair Protein Msh2 Is Necessary for Macronuclear Stability and Micronuclear Division in Tetrahymena thermophila.
Wang L, Xue Y, Yang S, Bo T, Xu J, Wang W. Wang L, et al. Int J Mol Sci. 2023 Jun 23;24(13):10559. doi: 10.3390/ijms241310559. Int J Mol Sci. 2023. PMID: 37445734 Free PMC article.
Molecular dynamics of mismatch detection-How MutS uses indirect readout to find errors in DNA.
Jayaraj A, Thayer KM, Beveridge DL, Hingorani MM. Jayaraj A, et al. Biophys J. 2023 Aug 8;122(15):3031-3043. doi: 10.1016/j.bpj.2023.06.006. Epub 2023 Jun 15. Biophys J. 2023. PMID: 37329136 Free PMC article.
Cryogenic electron microscopy structures reveal how ATP and DNA binding in MutS coordinates sequential steps of DNA mismatch repair.
Borsellini A, Kunetsky V, Friedhoff P, Lamers MH. Borsellini A, et al. Nat Struct Mol Biol. 2022 Jan;29(1):59-66. doi: 10.1038/s41594-021-00707-1. Epub 2022 Jan 10. Nat Struct Mol Biol. 2022. PMID: 35013597
Role of mismatch repair in aging.
Wen J, Wang Y, Yuan M, Huang Z, Zou Q, Pu Y, Zhao B, Cai Z. Wen J, et al. Int J Biol Sci. 2021 Sep 21;17(14):3923-3935. doi: 10.7150/ijbs.64953. eCollection 2021. Int J Biol Sci. 2021. PMID: 34671209 Free PMC article. Review.
Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin.
Kim JM, Visanpattanasin P, Jou V, Liu S, Tang X, Zheng Q, Li KY, Snedeker J, Lavis LD, Lionnet T, Wu C. Kim JM, et al. Elife. 2021 Jul 27;10:e69387. doi: 10.7554/eLife.69387. Elife. 2021. PMID: 34313223 Free PMC article.

Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA - PubMed (original) (raw)