Recurrent mismatch binding by MutS mobile clamps on DNA localizes repair complexes nearby

Proceedings of the National Academy of Sciences of the United States of America
Pengyu HaoKeith R Weninger

Abstract

DNA mismatch repair (MMR), the guardian of the genome, commences when MutS identifies a mismatch and recruits MutL to nick the error-containing strand, allowing excision and DNA resynthesis. Dominant MMR models posit that after mismatch recognition, ATP converts MutS to a hydrolysis-independent, diffusive mobile clamp that no longer recognizes the mismatch. Little is known about the postrecognition MutS mobile clamp and its interactions with MutL. Two disparate frameworks have been proposed: One in which MutS-MutL complexes remain mobile on the DNA, and one in which MutL stops MutS movement. Here we use single-molecule FRET to follow the postrecognition states of MutS and the impact of MutL on its properties. In contrast to current thinking, we find that after the initial mobile clamp formation event, MutS undergoes frequent cycles of mismatch rebinding and mobile clamp reformation without releasing DNA. Notably, ATP hydrolysis is required to alter the conformation of MutS such that it can recognize the mismatch again instead of bypassing it; thus, ATP hydrolysis licenses the MutS mobile clamp to rebind the mismatch. Moreover, interaction with MutL can both trap MutS at the mismatch en route to mobile clamp formation and stop m...Continue Reading

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References

Jan 1, 1996·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·N YaoM O'Donnell
Jul 16, 1997·The EMBO Journal·D J AllenJ D Griffith
May 24, 2001·The Journal of Biological Chemistry·M J SchofieldP Hsieh
Jul 7, 2001·The Journal of Biological Chemistry·L J BlackwellP Modrich
Jul 31, 2003·Molecular Cell·Samir AcharyaRichard Fishel
Dec 4, 2003·Journal of Molecular Biology·Tassadite SelmanePeggy Hsieh
Jun 15, 2005·Annual Review of Biochemistry·Thomas A Kunkel, Dorothy A Erie
Feb 9, 2006·Chemical Reviews·Ravi R IyerPaul L Modrich
Apr 14, 2006·Nature Reviews. Molecular Cell Biology·Josef Jiricny
Jul 29, 2006·Cell·Farid A KadyrovPaul Modrich
Nov 3, 2006·The Journal of Physical Chemistry. B·Eyal NirShimon Weiss
Jan 9, 2007·Journal of Molecular Biology·Emily Jacobs-Palmer, Manju M Hingorani
Oct 24, 2007·The Journal of Biological Chemistry·Farid A KadyrovPaul Modrich
Apr 15, 2008·Mechanisms of Ageing and Development·Peggy Hsieh, Kazuhiko Yamane
May 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Farid A KadyrovPaul Modrich
Feb 20, 2010·The Journal of Biological Chemistry·Joyce H G LebbinkTitia K Sixma
Feb 26, 2010·Biochemistry·Lauryn E SassDorothy A Erie
Jun 25, 2010·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Yusdi SantosoAchillefs N Kapanidis
Aug 3, 2010·Current Biology : CB·Marina ElezMiroslav Radman
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anna PluciennikPaul Modrich
Feb 1, 2011·Nature Structural & Molecular Biology·Cherlhyun JeongJong-Bong Lee
Jun 12, 2012·Structure·Won-Ki ChoJong-Bong Lee
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jason GormanEric C Greene
Apr 3, 2013·Cold Spring Harbor Perspectives in Biology·Josef Jiricny
Apr 3, 2013·Familial Cancer·C Richard Boland, Henry T Lynch
Oct 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Greg L HuraJohn A Tainer
Feb 13, 2015·Nature Reviews. Cancer·Henry T LynchMegan P Hitchins
Apr 12, 2015·Chromosoma·Gloria X ReyesHans Hombauer
Aug 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ruoyi QiuKeith R Weninger
Sep 8, 2015·Research in Microbiology·Justin S LenhartLyle A Simmons

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Citations

Jun 27, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kira C BradfordDorothy A Erie
Aug 6, 2020·Proceedings of the National Academy of Sciences of the United States of America·Christopher D Putnam
Sep 11, 2021·The Journal of Physical Chemistry. B·Narendar KolimiJoshua Alper
Nov 16, 2021·Journal of Chemical Information and Modeling·Tomáš BouchalPetr Kulhánek

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