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• W2892024408 abstract "DNA mismatch repair (MMR) corrects mispaired DNA bases and small insertion/deletion loops generated by DNA replication errors. After binding a mispair, the eukaryotic mispair recognition complex Msh2–Msh6 binds ATP in both of its nucleotide-binding sites, which induces a conformational change resulting in the formation of an Msh2–Msh6 sliding clamp that releases from the mispair and slides freely along the DNA. However, the roles that Msh2–Msh6 sliding clamps play in MMR remain poorly understood. Here, using Saccharomyces cerevisiae, we created Msh2 and Msh6 Walker A nucleotide–binding site mutants that have defects in ATP binding in one or both nucleotide-binding sites of the Msh2–Msh6 heterodimer. We found that these mutations cause a complete MMR defect in vivo. The mutant Msh2–Msh6 complexes exhibited normal mispair recognition and were proficient at recruiting the MMR endonuclease Mlh1–Pms1 to mispaired DNA. At physiological (2.5 mm) ATP concentration, the mutant complexes displayed modest partial defects in supporting MMR in reconstituted Mlh1–Pms1-independent and Mlh1–Pms1-dependent MMR reactions in vitro and in activation of the Mlh1–Pms1 endonuclease and showed a more severe defect at low (0.1 mm) ATP concentration. In contrast, five of the mutants were completely defective and one was mostly defective for sliding clamp formation at high and low ATP concentrations. These findings suggest that mispair-dependent sliding clamp formation triggers binding of additional Msh2–Msh6 complexes and that further recruitment of additional downstream MMR proteins is required for signal amplification of mispair binding during MMR. DNA mismatch repair (MMR) corrects mispaired DNA bases and small insertion/deletion loops generated by DNA replication errors. After binding a mispair, the eukaryotic mispair recognition complex Msh2–Msh6 binds ATP in both of its nucleotide-binding sites, which induces a conformational change resulting in the formation of an Msh2–Msh6 sliding clamp that releases from the mispair and slides freely along the DNA. However, the roles that Msh2–Msh6 sliding clamps play in MMR remain poorly understood. Here, using Saccharomyces cerevisiae, we created Msh2 and Msh6 Walker A nucleotide–binding site mutants that have defects in ATP binding in one or both nucleotide-binding sites of the Msh2–Msh6 heterodimer. We found that these mutations cause a complete MMR defect in vivo. The mutant Msh2–Msh6 complexes exhibited normal mispair recognition and were proficient at recruiting the MMR endonuclease Mlh1–Pms1 to mispaired DNA. At physiological (2.5 mm) ATP concentration, the mutant complexes displayed modest partial defects in supporting MMR in reconstituted Mlh1–Pms1-independent and Mlh1–Pms1-dependent MMR reactions in vitro and in activation of the Mlh1–Pms1 endonuclease and showed a more severe defect at low (0.1 mm) ATP concentration. In contrast, five of the mutants were completely defective and one was mostly defective for sliding clamp formation at high and low ATP concentrations. These findings suggest that mispair-dependent sliding clamp formation triggers binding of additional Msh2–Msh6 complexes and that further recruitment of additional downstream MMR proteins is required for signal amplification of mispair binding during MMR. DNA mismatch repair (MMR) 2The abbreviations used are: MMRmismatch repairPCNAproliferating cell nuclear antigenSPRsurface plasmon resonanceRUresponse unitsIPTGisopropyl 1-thio-β-d-galactopyranosideRFCreplication factor CSCsynthetic completeAMP-PNPadenosine 5′-(β,γ-imino)triphosphateMSHMutS Homolog. is a conserved pathway that repairs mispaired bases that result from errors during DNA synthesis (1Fishel R. Mismatch repair.J. Biol. Chem. 2015; 290 (26354434): 26395-2640310.1074/jbc.R115.660142Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar2Li Z. Pearlman A.H. Hsieh P. DNA mismatch repair and the DNA damage response.DNA Repair. 2016; 38 (26704428): 94-10110.1016/j.dnarep.2015.11.019Crossref PubMed Scopus (181) Google Scholar, 3Kolodner R.D. Marsischky G.T. Eukaryotic DNA mismatch repair.Curr. Opin. Genet. Dev. 1999; 9 (10072354): 89-9610.1016/S0959-437X(99)80013-6Crossref PubMed Scopus (724) Google Scholar, 4Li G.M. Mechanisms and functions of DNA mismatch repair.Cell Res. 2008; 18 (18157157): 85-9810.1038/cr.2007.115Crossref PubMed Scopus (865) Google Scholar, 5Spies M. Fishel R. Mismatch repair during homologous and homologous recombination.Cold Spring Harb. Perspect. Biol. 2015; 7 (25731766)a02265710.1101/cshperspect.a022657Crossref PubMed Scopus (95) Google Scholar6Jiricny J. Postreplicative mismatch repair.Cold Spring Harb. Perspect. Biol. 2013; 5 (23545421)a01263310.1101/cshperspect.a012633Crossref PubMed Scopus (224) Google Scholar). MMR also acts on some forms of chemically damaged DNA bases as well as on mispairs present in heteroduplex DNA intermediates formed during recombination (1Fishel R. Mismatch repair.J. Biol. Chem. 2015; 290 (26354434): 26395-2640310.1074/jbc.R115.660142Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar2Li Z. Pearlman A.H. Hsieh P. DNA mismatch repair and the DNA damage response.DNA Repair. 2016; 38 (26704428): 94-10110.1016/j.dnarep.2015.11.019Crossref PubMed Scopus (181) Google Scholar, 3Kolodner R.D. Marsischky G.T. Eukaryotic DNA mismatch repair.Curr. Opin. Genet. Dev. 1999; 9 (10072354): 89-9610.1016/S0959-437X(99)80013-6Crossref PubMed Scopus (724) Google Scholar, 4Li G.M. Mechanisms and functions of DNA mismatch repair.Cell Res. 2008; 18 (18157157): 85-9810.1038/cr.2007.115Crossref PubMed Scopus (865) Google Scholar, 5Spies M. Fishel R. Mismatch repair during homologous and homologous recombination.Cold Spring Harb. Perspect. Biol. 2015; 7 (25731766)a02265710.1101/cshperspect.a022657Crossref PubMed Scopus (95) Google Scholar6Jiricny J. Postreplicative mismatch repair.Cold Spring Harb. Perspect. Biol. 2013; 5 (23545421)a01263310.1101/cshperspect.a012633Crossref PubMed Scopus (224) Google Scholar). MMR proteins also act in a pathway that suppresses recombination between homologous but divergent DNAs (1Fishel R. Mismatch repair.J. Biol. Chem. 2015; 290 (26354434): 26395-2640310.1074/jbc.R115.660142Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar2Li Z. Pearlman A.H. Hsieh P. DNA mismatch repair and the DNA damage response.DNA Repair. 2016; 38 (26704428): 94-10110.1016/j.dnarep.2015.11.019Crossref PubMed Scopus (181) Google Scholar, 3Kolodner R.D. Marsischky G.T. Eukaryotic DNA mismatch repair.Curr. Opin. Genet. Dev. 1999; 9 (10072354): 89-9610.1016/S0959-437X(99)80013-6Crossref PubMed Scopus (724) Google Scholar, 4Li G.M. Mechanisms and functions of DNA mismatch repair.Cell Res. 2008; 18 (18157157): 85-9810.1038/cr.2007.115Crossref PubMed Scopus (865) Google Scholar, 5Spies M. Fishel R. Mismatch repair during homologous and homologous recombination.Cold Spring Harb. Perspect. Biol. 2015; 7 (25731766)a02265710.1101/cshperspect.a022657Crossref PubMed Scopus (95) Google Scholar6Jiricny J. Postreplicative mismatch repair.Cold Spring Harb. Perspect. Biol. 2013; 5 (23545421)a01263310.1101/cshperspect.a012633Crossref PubMed Scopus (224) Google Scholar) and function in a DNA damage response pathway for different types of DNA-damaging agents, including some chemotherapeutic agents (2Li Z. Pearlman A.H. Hsieh P. DNA mismatch repair and the DNA damage response.DNA Repair. 2016; 38 (26704428): 94-10110.1016/j.dnarep.2015.11.019Crossref PubMed Scopus (181) Google Scholar). As a result of the role that MMR plays in correcting mispairs, mutations in or loss of expression of MMR genes results in increased mutation rates that underlie both sporadic cancers and inherited cancer predisposition syndromes in humans (7Lynch H.T. Snyder C.L. Shaw T.G. Heinen C.D. Hitchins M.P. Milestones of Lynch syndrome: 1895–2015.Nat. Rev. Cancer. 2015; 15 (25673086): 181-19410.1038/nrc3878Crossref PubMed Scopus (456) Google Scholar8Durno C.A. Sherman P.M. Aronson M. Malkin D. Hawkins C. Bakry D. Bouffet E. Gallinger S. Pollett A. Campbell B. Tabori U. International BMMRD ConsortiumPhenotypic and genotypic characterisation of biallelic mismatch repair deficiency (BMMR-D) syndrome.Eur. J. Cancer. 2015; 51 (25883011): 977-98310.1016/j.ejca.2015.02.008Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar, 9Waterfall J.J. Meltzer P.S. Avalanching mutations in biallelic mismatch repair deficiency syndrome.Nat. Genet. 2015; 47 (25711864): 194-19610.1038/ng.3227Crossref PubMed Scopus (5) Google Scholar, 10Kane M.F. Loda M. Gaida G.M. Lipman J. Mishra R. Goldman H. Jessup J.M. Kolodner R. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.Cancer Res. 1997; 57 (9041175): 808-811PubMed Google Scholar11Syngal S. Fox E.A. Li C. Dovidio M. Eng C. Kolodner R.D. Garber J.E. Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer: implications for clinical predisposition testing.JAMA. 1999; 282 (10422993): 247-25310.1001/jama.282.3.247Crossref PubMed Scopus (126) Google Scholar). mismatch repair proliferating cell nuclear antigen surface plasmon resonance response units isopropyl 1-thio-β-d-galactopyranoside replication factor C synthetic complete adenosine 5′-(β,γ-imino)triphosphate MutS Homolog. The initiation of MMR in eukaryotes relies upon the recognition of DNA mispairs by the partially redundant Msh2–Msh6 and Msh2–Msh3 heterodimers, which are homologs of the bacterial MutS homodimer (1Fishel R. Mismatch repair.J. Biol. Chem. 2015; 290 (26354434): 26395-2640310.1074/jbc.R115.660142Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar, 3Kolodner R.D. Marsischky G.T. Eukaryotic DNA mismatch repair.Curr. Opin. Genet. Dev. 1999; 9 (10072354): 89-9610.1016/S0959-437X(99)80013-6Crossref PubMed Scopus (724) Google Scholar, 12Marsischky G.T. Filosi N. Kane M.F. Kolodner R. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair.Genes Dev. 1996; 10 (8600025): 407-42010.1101/gad.10.4.407Crossref PubMed Scopus (498) Google Scholar). Msh2–Msh6, Msh2–Msh3, and MutS belong to the ABC family of ATPases and have two composite nucleotide-binding sites at their dimeric interface (13Obmolova G. Ban C. Hsieh P. Yang W. Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA.Nature. 2000; 407 (11048710): 703-71010.1038/35037509Crossref PubMed Scopus (552) Google Scholar14Lamers M.H. Perrakis A. Enzlin J.H. Winterwerp H.H. de Wind N. Sixma T.K. The crystal structure of DNA mismatch repair protein MutS binding to a G·T mismatch.Nature. 2000; 407 (11048711): 711-71710.1038/35037523Crossref PubMed Scopus (549) Google Scholar, 15Gorbalenya A.E. Koonin E.V. Superfamily of UvrA-related NTP-binding proteins. Implications for rational classification of recombination/repair systems.J. Mol. Biol. 1990; 213 (2162963): 583-59110.1016/S0022-2836(05)80243-8Crossref PubMed Scopus (101) Google Scholar, 16Gupta S. Gellert M. Yang W. Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops.Nat. Struct. Mol. Biol. 2011; 19 (22179786): 72-7810.1038/nsmb.2175Crossref PubMed Scopus (107) Google Scholar17Warren J.J. Pohlhaus T.J. Changela A. Iyer R.R. Modrich P.L. Beese L.S. Structure of the human MutSα DNA lesion recognition complex.Mol. Cell. 2007; 26 (17531815): 579-59210.1016/j.molcel.2007.04.018Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar). Each composite nucleotide-binding site comprises the Walker A and Walker B motifs from one subunit and the “signature” motif from the other subunit (18Hopfner K.P. Tainer J.A. Rad50/SMC proteins and ABC transporters: unifying concepts from high-resolution structures.Curr. Opin. Struct. Biol. 2003; 13 (12727520): 249-25510.1016/S0959-440X(03)00037-XCrossref PubMed Scopus (171) Google Scholar, 19Jones P.M. George A.M. Mechanism of the ABC transporter ATPase domains: catalytic models and the biochemical and biophysical record.Crit. Rev. Biochem. Mol. Biol. 2013; 48 (23131203): 39-5010.3109/10409238.2012.735644Crossref PubMed Scopus (50) Google Scholar20Haber L.T. Walker G.C. Altering the conserved nucleotide binding motif in the Salmonella typhimurium MutS mismatch repair protein affects both its ATPase and mismatch binding activities.EMBO J. 1991; 10 (1651234): 2707-271510.1002/j.1460-2075.1991.tb07815.xCrossref PubMed Scopus (134) Google Scholar). In the MSH complexes, of which Msh2–Msh6 has been the most extensively studied, ATP binding, ATP hydrolysis, and ADP release are intrinsically linked to conformational changes that play critical roles in MMR (20Haber L.T. Walker G.C. Altering the conserved nucleotide binding motif in the Salmonella typhimurium MutS mismatch repair protein affects both its ATPase and mismatch binding activities.EMBO J. 1991; 10 (1651234): 2707-271510.1002/j.1460-2075.1991.tb07815.xCrossref PubMed Scopus (134) Google Scholar21Hargreaves V.V. Shell S.S. Mazur D.J. Hess M.T. Kolodner R.D. Interaction between the Msh2 and Msh6 nucleotide-binding sites in the Saccharomyces cerevisiae Msh2-Msh6 complex.J. Biol. Chem. 2010; 285 (20089866): 9301-931010.1074/jbc.M109.096388Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 22Mendillo M.L. Mazur D.J. Kolodner R.D. Analysis of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 and MLH1-PMS1 complexes with DNA using a reversible DNA end-blocking system.J. Biol. Chem. 2005; 280 (15811858): 22245-2225710.1074/jbc.M407545200Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar, 23Gradia S. Acharya S. Fishel R. The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch.Cell. 1997; 91 (9428522): 995-100510.1016/S0092-8674(00)80490-0Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar, 24Mazur D.J. Mendillo M.L. Kolodner R.D. Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA.Mol. Cell. 2006; 22 (16600868): 39-4910.1016/j.molcel.2006.02.010Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 25Antony E. Hingorani M.M. Asymmetric ATP binding and hydrolysis activity of the Thermus aquaticus MutS dimer is key to modulation of its interactions with mismatched DNA.Biochemistry. 2004; 43 (15476405): 13115-1312810.1021/bi049010tCrossref PubMed Scopus (57) Google Scholar, 26Antony E. Hingorani M.M. Mismatch recognition-coupled stabilization of Msh2-Msh6 in an ATP-bound state at the initiation of DNA repair.Biochemistry. 2003; 42 (12820877): 7682-769310.1021/bi034602hCrossref PubMed Scopus (81) Google Scholar, 27Antony E. Khubchandani S. Chen S. Hingorani M.M. Contribution of Msh2 and Msh6 subunits to the asymmetric ATPase and DNA mismatch binding activities of Saccharomyces cerevisiae Msh2-Msh6 mismatch repair protein.DNA Repair. 2006; 5 (16214425): 153-16210.1016/j.dnarep.2005.08.016Crossref PubMed Scopus (38) Google Scholar, 28Studamire B. Quach T. Alani E. Saccharomyces cerevisiae Msh2p and Msh6p ATPase activities are both required during mismatch repair.Mol. Cell. Biol. 1998; 18 (9819445): 7590-760110.1128/MCB.18.12.7590Crossref PubMed Scopus (81) Google Scholar, 29Groothuizen F.S. Winkler I. Cristóvão M. Fish A. Winterwerp H.H. Reumer A. Marx A.D. Hermans N. Nicholls R.A. Murshudov G.N. Lebbink J.H. Friedhoff P. Sixma T.K. MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA.Elife. 2015; 4 (26163658)e0674410.7554/eLife.06744Crossref PubMed Google Scholar, 30Hess M.T. Mendillo M.L. Mazur D.J. Kolodner R.D. Biochemical basis for dominant mutations in the Saccharomyces cerevisiae MSH6 gene.Proc. Natl. Acad. Sci. U.S.A. 2006; 103 (16407100): 558-56310.1073/pnas.0510078103Crossref PubMed Scopus (25) Google Scholar, 31Srivatsan A. Bowen N. Kolodner R.D. Mispair-specific recruitment of the Mlh1-Pms1 complex identifies repair substrates of the Saccharomyces cerevisiae Msh2-Msh3 complex.J. Biol. Chem. 2014; 289 (24550389): 9352-936410.1074/jbc.M114.552190Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 32Gradia S. Subramanian D. Wilson T. Acharya S. Makhov A. Griffith J. Fishel R. hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA.Mol. Cell. 1999; 3 (10078208): 255-26110.1016/S1097-2765(00)80316-0Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar, 33Wilson T. Guerrette S. Fishel R. Dissociation of mismatch recognition and ATPase activity by hMSH2-hMSH3.J. Biol. Chem. 1999; 274 (10419475): 21659-2166410.1074/jbc.274.31.21659Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar34Jeong C. Cho W.K. Song K.M. Cook C. Yoon T.Y. Ban C. Fishel R. Lee J.B. MutS switches between two fundamentally distinct clamps during mismatch repair.Nat. Struct. Mol. Biol. 2011; 18 (21278758): 379-38510.1038/nsmb.2009Crossref PubMed Scopus (100) Google Scholar). In the Msh2–Msh6 complex, the Msh6 subunit, which directly interacts with the mispair, has the higher affinity for ATP (∼10-fold higher than Msh2), whereas the Msh2 subunit has the higher affinity for ADP (24Mazur D.J. Mendillo M.L. Kolodner R.D. Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA.Mol. Cell. 2006; 22 (16600868): 39-4910.1016/j.molcel.2006.02.010Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar). Similarly, the homodimeric bacterial MutS, which adopts an asymmetric conformation upon mispair recognition (13Obmolova G. Ban C. Hsieh P. Yang W. Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA.Nature. 2000; 407 (11048710): 703-71010.1038/35037509Crossref PubMed Scopus (552) Google Scholar, 14Lamers M.H. Perrakis A. Enzlin J.H. Winterwerp H.H. de Wind N. Sixma T.K. The crystal structure of DNA mismatch repair protein MutS binding to a G·T mismatch.Nature. 2000; 407 (11048711): 711-71710.1038/35037523Crossref PubMed Scopus (549) Google Scholar), also has ATP binding asymmetries (25Antony E. Hingorani M.M. Asymmetric ATP binding and hydrolysis activity of the Thermus aquaticus MutS dimer is key to modulation of its interactions with mismatched DNA.Biochemistry. 2004; 43 (15476405): 13115-1312810.1021/bi049010tCrossref PubMed Scopus (57) Google Scholar, 35Worth Jr., L. Bader T. Yang J. Clark S. Role of MutS ATPase activity in MutS,L-dependent block of in vitro strand transfer.J. Biol. Chem. 1998; 273 (9722547): 23176-2318210.1074/jbc.273.36.23176Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar, 36Monti M.C. Cohen S.X. Fish A. Winterwerp H.H. Barendregt A. Friedhoff P. Perrakis A. Heck A.J. Sixma T.K. van den Heuvel R.H. Lebbink J.H. Native mass spectrometry provides direct evidence for DNA mismatch-induced regulation of asymmetric nucleotide binding in mismatch repair protein MutS.Nucleic Acids Res. 2011; 39 (21737427): 8052-806410.1093/nar/gkr498Crossref PubMed Scopus (29) Google Scholar). In both human and Saccharomyces cerevisiae Msh2–Msh6, the Msh2 subunit controls the cycle of ATP processing. After Msh2–Msh6 binds mispaired DNA, release of Mg2+ from the Msh2 nucleotide-binding site causes release of ADP from Msh2, which then allows Msh6 to bind ATP (23Gradia S. Acharya S. Fishel R. The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch.Cell. 1997; 91 (9428522): 995-100510.1016/S0092-8674(00)80490-0Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar, 24Mazur D.J. Mendillo M.L. Kolodner R.D. Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA.Mol. Cell. 2006; 22 (16600868): 39-4910.1016/j.molcel.2006.02.010Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 37Heinen C.D. Cyr J.L. Cook C. Punja N. Sakato M. Forties R.A. Lopez J.M. Hingorani M.M. Fishel R. Human MSH2 (hMSH2) protein controls ATP processing by hMSH2-hMSH6.J. Biol. Chem. 2011; 286 (21937421): 40287-4029510.1074/jbc.M111.297523Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar). In turn, ATP binding to the Msh6 nucleotide-binding site results in reduced affinity of the Msh2 nucleotide-binding site for ADP, causing Msh2 to favor binding of ATP (24Mazur D.J. Mendillo M.L. Kolodner R.D. Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA.Mol. Cell. 2006; 22 (16600868): 39-4910.1016/j.molcel.2006.02.010Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar). Msh2–Msh6 binding to mispaired DNA also results in a reduction of the ATPase activity of Msh6 (26Antony E. Hingorani M.M. Mismatch recognition-coupled stabilization of Msh2-Msh6 in an ATP-bound state at the initiation of DNA repair.Biochemistry. 2003; 42 (12820877): 7682-769310.1021/bi034602hCrossref PubMed Scopus (81) Google Scholar). When Msh2–Msh6 and other members of the MutS family of MMR proteins bind to mispaired bases, they form a ring around the DNA with the mispair recognition domain of Msh6 (or Msh3 or the mispair-binding subunit of MutS) making contacts with both the mispair and adjacent sites on the DNA; these contacts also result in bending of the DNA (13Obmolova G. Ban C. Hsieh P. Yang W. Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA.Nature. 2000; 407 (11048710): 703-71010.1038/35037509Crossref PubMed Scopus (552) Google Scholar, 14Lamers M.H. Perrakis A. Enzlin J.H. Winterwerp H.H. de Wind N. Sixma T.K. The crystal structure of DNA mismatch repair protein MutS binding to a G·T mismatch.Nature. 2000; 407 (11048711): 711-71710.1038/35037523Crossref PubMed Scopus (549) Google Scholar, 16Gupta S. Gellert M. Yang W. Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops.Nat. Struct. Mol. Biol. 2011; 19 (22179786): 72-7810.1038/nsmb.2175Crossref PubMed Scopus (107) Google Scholar, 17Warren J.J. Pohlhaus T.J. Changela A. Iyer R.R. Modrich P.L. Beese L.S. Structure of the human MutSα DNA lesion recognition complex.Mol. Cell. 2007; 26 (17531815): 579-59210.1016/j.molcel.2007.04.018Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar, 38Hura G.L. Tsai C.L. Claridge S.A. Mendillo M.L. Smith J.M. Williams G.J. Mastroianni A.J. Alivisatos A.P. Putnam C.D. Kolodner R.D. Tainer J.A. DNA conformations in mismatch repair probed in solution by X-ray scattering from gold nanocrystals.Proc. Natl. Acad. Sci. U.S.A. 2013; 110 (24101514): 17308-1731310.1073/pnas.1308595110Crossref PubMed Scopus (49) Google Scholar, 39Wang H. Yang Y. Schofield M.J. Du C. Fridman Y. Lee S.D. Larson E.D. Drummond J.T. Alani E. Hsieh P. Erie D.A. DNA bending and unbending by MutS govern mismatch recognition and specificity.Proc. Natl. Acad. Sci. U.S.A. 2003; 100 (14634210): 14822-1482710.1073/pnas.2433654100Crossref PubMed Scopus (162) Google Scholar). ATP binding by mispair-bound Msh2–Msh6 and other MutS family members induces a number of conformational changes in the protein complex: 1) the DNA mispair recognition domain and the connector domain become exposed (29Groothuizen F.S. Winkler I. Cristóvão M. Fish A. Winterwerp H.H. Reumer A. Marx A.D. Hermans N. Nicholls R.A. Murshudov G.N. Lebbink J.H. Friedhoff P. Sixma T.K. MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA.Elife. 2015; 4 (26163658)e0674410.7554/eLife.06744Crossref PubMed Google Scholar, 40Mendillo M.L. Hargreaves V.V. Jamison J.W. Mo A.O. Li S. Putnam C.D. Woods Jr, V.L. Kolodner R.D. A conserved MutS homolog connector domain interface interacts with MutL homologs.Proc. Natl. Acad. Sci. U.S.A. 2009; 106 (20080788): 22223-2222810.1073/pnas.0912250106Crossref PubMed Scopus (66) Google Scholar), and 2) upon binding ATP in both ATP-binding sites, Msh2–Msh6 and other MutS family proteins transition into a sliding clamp form that dissociates from the mispair, alleviates the DNA bend at the mispair, and slides along the DNA (22Mendillo M.L. Mazur D.J. Kolodner R.D. Analysis of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 and MLH1-PMS1 complexes with DNA using a reversible DNA end-blocking system.J. Biol. Chem. 2005; 280 (15811858): 22245-2225710.1074/jbc.M407545200Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar, 23Gradia S. Acharya S. Fishel R. The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch.Cell. 1997; 91 (9428522): 995-100510.1016/S0092-8674(00)80490-0Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar24Mazur D.J. Mendillo M.L. Kolodner R.D. Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement along DNA.Mol. Cell. 2006; 22 (16600868): 39-4910.1016/j.molcel.2006.02.010Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 31Srivatsan A. Bowen N. Kolodner R.D. Mispair-specific recruitment of the Mlh1-Pms1 complex identifies repair substrates of the Saccharomyces cerevisiae Msh2-Msh3 complex.J. Biol. Chem. 2014; 289 (24550389): 9352-936410.1074/jbc.M114.552190Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 32Gradia S. Subramanian D. Wilson T. Acharya S. Makhov A. Griffith J. Fishel R. hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA.Mol. Cell. 1999; 3 (10078208): 255-26110.1016/S1097-2765(00)80316-0Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar33Wilson T. Guerrette S. Fishel R. Dissociation of mismatch recognition and ATPase activity by hMSH2-hMSH3.J. Biol. Chem. 1999; 274 (10419475): 21659-2166410.1074/jbc.274.31.21659Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 38Hura G.L. Tsai C.L. Claridge S.A. Mendillo M.L. Smith J.M. Williams G.J. Mastroianni A.J. Alivisatos A.P. Putnam C.D. Kolodner R.D. Tainer J.A. DNA conformations in mismatch repair probed in solution by X-ray scattering from gold nanocrystals.Proc. Natl. Acad. Sci. U.S.A. 2013; 110 (24101514): 17308-1731310.1073/pnas.1308595110Crossref PubMed Scopus (49) Google Scholar, 41Liu J. Hanne J. Britton B.M. Bennett J. Kim D. Lee J.B. Fishel R. Cascading MutS and MutL sliding clamps control DNA diffusion to activate mismatch repair.Nature. 2016; 539 (27851738): 583-58710.1038/nature20562Crossref PubMed Scopus (72) Google Scholar, 42Cho W.K. Jeong C. Kim D. Chang M. Song K.M. Hanne J. Ban C. Fishel R. Lee J.B. ATP alters the diffusion mechanics of MutS on mismatched DNA.Structure. 2012; 20 (22682745): 1264-127410.1016/j.str.2012.04.017Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar43Acharya S. Foster P.L. Brooks P. Fishel R. The coordinated functions of the E. coli MutS and MutL proteins in mismatch repair.Mol. Cell. 2003; 12 (12887908): 233-24610.1016/S1097-2765(03)00219-3Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar). In addition, mispair and ATP binding by Msh2–Msh6 results in recruitment of the MutL homolog complexes Mlh1–Pms1 and Mlh1–Mlh2 by the newly exposed surfaces on the connector domain of Msh2 (29Groothuizen F.S. Winkler I. Cristóvão M. Fish A. Winterwerp H.H. Reumer A. Marx A.D. Hermans N. Nicholls R.A. Murshudov G.N. Lebbink J.H. Friedhoff P. Sixma T.K. MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA.Elife. 2015; 4 (26163658)e0674410.7554/eLife.06744Crossref PubMed Google Scholar, 40Mendillo M.L. Hargreaves V.V. Jamison J.W. Mo A.O. Li S. Putnam C.D. Woods Jr, V.L. Kolodner R.D. A conserved MutS homolog connector domain interface interacts with MutL homologs.Proc. Natl. Acad. Sci. U.S.A. 2009; 106 (20080788): 22223-2222810.1073/pnas.0912250106Crossref PubMed Scopus (66) Google Scholar), which then appears to allow loading of Mlh1–Pms1 and Mlh1–Mlh2 onto the DNA and can mediate the formation of a MutL-based sliding clamp (31Srivatsan A. Bowen N. Kolodner R.D. Mispair-specific recruitment of the Mlh1-Pms1 complex identifies repair substrates of the Saccharomyces cerevisiae Msh2-Msh3 complex.J. Biol. Chem. 2014; 289 (24550389): 9352-936410.1074/jbc.M114.552190Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 41Liu J. Hanne J. Britton B.M. Bennett J. Kim D. Lee J.B. Fishel R. Cascading MutS and MutL sliding clamps control DNA diffusion to activate mismatch repair.Nature. 2016; 539 (27851738): 583-58710.1038/nature20562Crossref PubMed Scopus (72) Google Scholar, 43Acharya S. Foster P.L. Brooks P. Fishel R. The coordinated functions of the E. coli MutS and MutL proteins in mismatch repair.Mol. Cell. 2003; 12 (12887908): 233-24610.1016/S1097-2765(03)00219-3Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar, 44Campbell C.S. Hombauer H. Srivatsan A. Bowen N. Gries K. Desai A. Putnam C.D. Kolodner R.D. Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae.PLoS Genet. 2014; 10 (24811092)e100432710.1371/journal.pgen.1004327Crossref PubMed Scopus (29) Google Scholar45Hombauer H. Campbell C.S. Smith C.E. Desai A. Kolodner R.D. Visualization of eukaryotic DNA mismatch repair reveals distinct recognition and repair intermediates.Cell. 2011; 147 (22118461): 1040-105310.1016/j.cell.2011.10.025Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar). However, studies of dominant MSH6 mutant Msh2–Msh6 complexes have suggested that recruitment of Mlh1–Pms1 by S. cerevisiae Msh2–Msh6 may not be completely dependent on the formation of Msh2–Msh6 sliding clamps (21Hargreaves V.V. Shell S.S. Mazur D.J. Hess M.T. Kolodner R.D. Interaction between the Msh2 and Msh6 nucleotide-binding sites in the Saccharomyces cerevisiae Msh2-Msh6 complex.J. Biol. Chem. 2010; 285 (20089866): 9301-931010.1074/jbc.M109.096388Abstract Full Text Full Text" @default.
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• W2892024408 title "The properties of Msh2–Msh6 ATP binding mutants suggest a signal amplification mechanism in DNA mismatch repair" @default.
• W2892024408 cites W122675378 @default.
• W2892024408 cites W1518834999 @default.
• W2892024408 cites W1554311327 @default.
• W2892024408 cites W1607945477 @default.
• W2892024408 cites W1925777748 @default.
• W2892024408 cites W1963802150 @default.
• W2892024408 cites W1979836109 @default.
• W2892024408 cites W1980179932 @default.
• W2892024408 cites W1983546592 @default.
• W2892024408 cites W1984467885 @default.
• W2892024408 cites W1985398661 @default.
• W2892024408 cites W1986555480 @default.
• W2892024408 cites W1990335933 @default.
• W2892024408 cites W1998495608 @default.
• W2892024408 cites W2002018134 @default.
• W2892024408 cites W2002108914 @default.
• W2892024408 cites W2003056152 @default.
• W2892024408 cites W2004297150 @default.
• W2892024408 cites W2010233450 @default.
• W2892024408 cites W2011456814 @default.
• W2892024408 cites W2011885375 @default.
• W2892024408 cites W2013735712 @default.
• W2892024408 cites W2016286342 @default.
• W2892024408 cites W2017483175 @default.
• W2892024408 cites W2018618332 @default.
• W2892024408 cites W2031142206 @default.
• W2892024408 cites W2035765657 @default.
• W2892024408 cites W2036690353 @default.
• W2892024408 cites W2038543541 @default.
• W2892024408 cites W2047433802 @default.
• W2892024408 cites W2050801122 @default.
• W2892024408 cites W2052442016 @default.
• W2892024408 cites W2054621069 @default.
• W2892024408 cites W2054758721 @default.
• W2892024408 cites W2054875504 @default.
• W2892024408 cites W2063847889 @default.
• W2892024408 cites W2067206133 @default.
• W2892024408 cites W2067443087 @default.
• W2892024408 cites W2072259400 @default.
• W2892024408 cites W2074322008 @default.
• W2892024408 cites W2074750127 @default.
• W2892024408 cites W2075182125 @default.
• W2892024408 cites W2076046893 @default.
• W2892024408 cites W2078319055 @default.
• W2892024408 cites W2079838148 @default.
• W2892024408 cites W2080930437 @default.
• W2892024408 cites W2081023620 @default.
• W2892024408 cites W2086264223 @default.
• W2892024408 cites W2089068108 @default.
• W2892024408 cites W2096331487 @default.
• W2892024408 cites W2096731080 @default.
• W2892024408 cites W2097225979 @default.
• W2892024408 cites W2099974826 @default.
• W2892024408 cites W2106826690 @default.
• W2892024408 cites W2113548088 @default.
• W2892024408 cites W2118641088 @default.
• W2892024408 cites W2121473677 @default.
• W2892024408 cites W2129039776 @default.
• W2892024408 cites W2133231925 @default.
• W2892024408 cites W2136615212 @default.
• W2892024408 cites W2137500337 @default.
• W2892024408 cites W2141323033 @default.
• W2892024408 cites W2143787623 @default.
• W2892024408 cites W2149852513 @default.
• W2892024408 cites W2154773687 @default.
• W2892024408 cites W2164015357 @default.
• W2892024408 cites W2166776471 @default.
• W2892024408 cites W2167244555 @default.
• W2892024408 cites W2170472485 @default.
• W2892024408 cites W2171461819 @default.
• W2892024408 cites W228873379 @default.
• W2892024408 cites W2295205936 @default.
• W2892024408 cites W2390421705 @default.
• W2892024408 cites W2551721425 @default.
• W2892024408 cites W2567554261 @default.
• W2892024408 cites W2593655047 @default.
• W2892024408 cites W2883274990 @default.
• W2892024408 cites W3142684927 @default.
• W2892024408 cites W4247581106 @default.
• W2892024408 cites W73080040 @default.
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