Dissociation of Mismatch Recognition and ATPase Activity by hMSH2-hMSH3*

MSH2-MSH3 directs the repair of insertion/deletion loops of up to 13 nucleotides in vivoand in vitro. To examine the biochemical basis of this repair specificity, we characterized the mispair binding and ATPase activity of hMSH2-hMSH3. The ATPase was found to be regulated by a mismatch-stimulated ADP → ATP exchange, which induces a conformational transition by the protein complex. We demonstrated strong binding of hMSH2-hMSH3 to an insertion/deletion loop containing 24 nucleotides that is incapable of provoking ADP → ATP exchange, suggesting that mismatch recognition appears to be necessary but not sufficient to induce the intrinsic ATPase. These studies support the idea that hMSH2-hMSH3 functions as an adenosine nucleotide-regulated molecular switch that must be activated by mismatched nucleotides for classical mismatch repair to occur.

• Publication year

  1999

• Venue

  Journal of Biological Chemistry

• Publication date

  1999-07-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.274.31.21659PMID 10419475
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA.

  1999cited by this paper
• Isolation of MutSbeta from human cells and comparison of the mismatch repair specificities of MutSbeta and MutSalpha.

  1998cited by this paper
• DNA-dependent Activation of the hMutSα ATPase*

  1998cited by this paper
• Isolation of MutSβ from Human Cells and Comparison of the Mismatch Repair Specificities of MutSβ and MutSα*

  1998cited by this paper
• Functional overlap in mismatch repair by human MSH3 and MSH6.

  1998cited by this paper
• Mismatch repair, molecular switches, and signal transduction.

  1998cited by this paper
• MutS homologs in mammalian cells.

  1997cited by this paper
• Genetic and biochemical analysis of Msh2p-Msh6p: role of ATP hydrolysis and Msh2p-Msh6p subunit interactions in mismatch base pair recognition

  1997cited by this paper
• The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch.

  1997cited by this paper
• de la Chapelle, A.

  1997cited by this paper
• Repair of DNA loops involves DNA-mismatch and nucleotide-excision repair proteins

  1997cited by this paper
• Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand break-induced recombination.

  1997cited by this paper
• Microsatellite instability in yeast: dependence on repeat unit size and DNA mismatch repair genes

  1997cited by this paper
• MutS mediates heteroduplex loop formation by a translocation mechanism

  1997cited by this paper
• Biochemistry and genetics of eukaryotic mismatch repair.

  1996cited by this paper
• Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair.

  1996cited by this paper
• Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3.

  1996cited by this paper
• hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6.

  1996cited by this paper
• The prevention of repeat-associated deletions in Saccharomyces cerevisiae by mismatch repair depends on size and origin of deletions.

  1996cited by this paper
• Mismatch repair in replication fidelity, genetic recombination, and cancer biology.

  1996cited by this paper
• Mismatch repair: mechanisms and relationship to cancer susceptibility.

  1995cited by this paper
• Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells.

  1995cited by this paper
• Identification of mismatch repair genes and their role in the development of cancer.

  1995cited by this paper
• Microsatellite instability: marker of a mutator phenotype in cancer.

  1994cited by this paper
• Binding of mismatched microsatellite DNA sequences by the human MSH2 protein.

  1994cited by this paper
• Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae.

  1994cited by this paper
• The effect of DNA mismatches on the ATPase activity of MSH1, a protein in yeast mitochondria that recognizes DNA mismatches.

  1994cited by this paper
• Microsatellite Instability: Marker of a Mutator Phenotype in Cancer

  1994cited by this paper
• Nucleotide repeats. Slippery DNA and diseases.

  1993cited by this paper
• Slippery DNA and diseases

  1993cited by this paper
• Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome.

  1993cited by this paper
• Emerging concepts in the Ras superfamily of GTP‐binding proteins

  1993cited by this paper
• Hypermutability and mismatch repair deficiency in RER+ tumor cells.

  1993cited by this paper
• Repair of DNA heteroduplexes containing small heterologous sequences in Escherichia coli.

  1992cited by this paper
• Heteroduplex repair in extracts of human HeLa cells.

  1991cited by this paper
• Altering the conserved nucleotide binding motif in the Salmonella typhimurium MutS mismatch repair protein affects both its ATPase and mismatch binding activities.

  1991cited by this paper
• Strand-specific mismatch correction in nuclear extracts of human and Drosophila melanogaster cell lines.

  1990cited by this paper
• Distantly related sequences in the alpha‐ and beta‐subunits of ATP synthase, myosin, kinases and other ATP‐requiring enzymes and a common nucleotide binding fold.

  1982cited by this paper
• Location of genes controlling excision repair of UV damage and mutator activity in Escherichia coli WP2.

  1970cited by this paper
• Genetic Location in Escherichia coli K-12 of the Ultraviolet-Sensitive Mutation uvrD3

  1970cited by this paper
• Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4

  1970cited by this paper
• Mutator Gene of Escherichia coli B

  1967cited by this paper
• Nonconservative DNA replication in bacteria after thymine starvation.

  1965cited by this paper
• PURE CLONES OF LACTOSE-NEGATIVE MUTANTS OBTAINED IN ESCHERICHIA COLI AFTER TREATMENT WITH 5-BROMOURACIL.

  1964cited by this paper
• Proline Mutants of Salmonella Typhimurium.

  1960cited by this paper

• Msh2-Msh3 DNA-binding is not sufficient to promote trinucleotide repeat expansions in Saccharomyces cerevisiae

  2024cites this paper
• New Discoveries on Protein Recruitment and Regulation during the Early Stages of the DNA Damage Response Pathways

  2024cites this paper
• Msh2-Msh3 interferes with DNA metabolism in vivo

  2023cites this paper
• Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo

  2023cites this paper
• Exploiting the distinctive properties of the bacterial and human MutS homolog sliding clamps on mismatched DNA

  2022influential citation
• The Formation of a Stable Sliding Clamp Discriminates MSH2-MSH3 and MSH2-MSH6 Mismatch Interaction

  2021cites this paper
• Coordinated roles of SLX4 and MutSβ in DNA repair and the maintenance of genome stability

  2021cites this paper
• DNA Mismatch Repair and its Role in Huntington’s Disease

  2021cites this paper
• MutSβ Stimulates Holliday Junction Resolution by the SMX Complex.

  2020cites this paper
• The double-edged sword of cancer mutations: exploiting neoepitopes for the fight against cancer.

  2019cites this paper
• MutL sliding clamps coordinate exonuclease-independent Escherichia coli mismatch repair

  2019cites this paper
• The properties of Msh2–Msh6 ATP binding mutants suggest a signal amplification mechanism in DNA mismatch repair

  2018cites this paper
• binding suggest a signal in mismatch repair.

  2018cites this paper
• Coordinating Multi-Protein Mismatch Repair by Managing Diffusion Mechanics on the DNA.

  2018cites this paper
• BIOCHEMICAL CHARACTERIZATION OF HUMAN MISMATCH RECOGNITION PROTEINS MUTSα AND MUTSβ

  2018cites this paper
• Stochastic Processes and Component Plasticity Governing DNA Mismatch Repair.

  2018cites this paper
• MutS homolog sliding clamps shield the DNA from binding proteins

  2018cites this paper
• Long-Range Signaling in MutS and MSH Homologs via Switching of Dynamic Communication Pathways

  2016cites this paper
• A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?

  2016cites this paper
• Mutations in the nucleotide binding and hydrolysis domains of Helicobacter pylori MutS2 lead to altered biochemical activities and inactivation of its in vivo function

  2016cites this paper
• Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions

  2016cites this paper
• Trinucleotide Repeat Instability Is Modulated by DNA Base Lesions and DNA Base Excision Repair

  2016cites this paper
• A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients.

  2016cites this paper
• Roles for mismatch repair family proteins in promoting meiotic crossing over.

  2016cites this paper
• A personal historical view of DNA mismatch repair with an emphasis on eukaryotic DNA mismatch repair.

  2016cites this paper
• Mismatch repair during homologous and homeologous recombination.

  2015influential citation
• Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System*

  2015cites this paper
• Mismatch Repair*

  2015cites this paper
• The Mismatch-Binding Factor MutSβ Can Mediate ATR Activation in Response to DNA Double-Strand Breaks.

  2015cites this paper
• DNA triplet repeat expansion and mismatch repair.

  2015cites this paper
• Mispair-specific Recruitment of the Mlh1-Pms1 Complex Identifies Repair Substrates of the Saccharomyces cerevisiae Msh2-Msh3 Complex*

  2014cites this paper
• ATP binding and hydrolysis by Saccharomyces cerevisiae Msh2-Msh3 are differentially modulated by mismatch and double-strand break repair DNA substrates.

  2014influential citation
• 2-Msh 3 Complex Saccharomyces cerevisiae Substrates of the Mlh 1-Pms 1 Complex Identifies Repair Mispair-specific Recruitment of the DNA and Chromosomes :

  2014cites this paper
• MOLECULAR MECHANISM OF HUMAN MISMATCH REPAIR INITIATION

  2014cites this paper
• Single-molecule views of MutS on mismatched DNA.

  2014cites this paper
• DNA Repair Mechanisms in Huntington’s Disease

  2013cites this paper
• Role of DNA Mismatch Repair in Disease-associated Trinucleotide Repeat Instability

  2013cites this paper
• Distinct requirements within the Msh3 nucleotide binding pocket for mismatch and double-strand break repair.

  2013cites this paper
• Reconstitution of long and short patch mismatch repair reactions using Saccharomyces cerevisiae proteins

  2013cites this paper
• Single-molecule FRET Studies on DNA Mismatch Repair

  2013cites this paper
• Engineered Disulfide-forming Amino Acid Substitutions Interfere with a Conformational Change in the Mismatch Recognition Complex Msh2-Msh6 Required for Mismatch Repair*

  2012cites this paper
• The predicted truncation from a cancer‐associated variant of the MSH2 initiation codon alters activity of the MSH2‐MSH6 mismatch repair complex

  2012cites this paper
• Defective DNA Mismatch Repair-dependent c-Abl-p73-GADD45α Expression Confers Cancer Chemoresistance

  2012cites this paper
• Required for Mismatch Repair Recognition Complex Msh 2-Msh 6 Conformational Change in the Mismatch Substitutions Interfere with a Engineered Disulfide-forming Amino Acid DNA and Chromosomes :

  2012cites this paper
• Conformational trapping of Mismatch Recognition Complex MSH2/MSH3 on repair-resistant DNA loops

  2011influential citation
• Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops

  2011cites this paper
• Making Sense of Missense in Lynch Syndrome: The Clinical Perspective

  2010cites this paper
• Magnesium Coordination Controls the Molecular Switch Function of DNA Mismatch Repair Protein MutS*

  2010cites this paper
• Continuous and Periodic Expansion of CAG Repeats in Huntington's Disease R6/1 Mice

  2010cites this paper
• Interaction between human mismatch repair recognition proteins and checkpoint sensor Rad9-Rad1-Hus1.

  2010cites this paper
• Interaction between the Msh2 and Msh6 Nucleotide-binding Sites in the Saccharomyces cerevisiae Msh2-Msh6 Complex*

  2010cites this paper
• Isolated short CTG/CAG DNA slip-outs are repaired efficiently by hMutSβ, but clustered slip-outs are poorly repaired

  2010cites this paper
• An epitome of DNA repair related genes and mechanisms in thyroid carcinoma.

  2010cites this paper
• Cis-elements Affecting Disease-associated Repeat Sequences

  2010cites this paper
• Biochemical characterization of human mismatch recognition proteins MUTSalpha and MUTSbeta

  2010cites this paper
• Functional Studies and Homology Modeling of Msh2-Msh3 Predict that Mispair Recognition Involves DNA Bending and Strand Separation

  2010cites this paper
• Mechanisms of mispair recognition by Msh2-Msh3

  2009influential citation
• The nucleotide binding dynamics of human MSH2–MSH3 are lesion dependent

  2009cites this paper
• DNA mismatch repair (MMR)‐dependent 5‐fluorouracil cytotoxicity and the potential for new therapeutic targets

  2009cites this paper
• Distinct Nucleotide Binding/Hydrolysis Properties and Molar Ratio of MutSα and MutSβ Determine Their Differential Mismatch Binding Activities*

  2009cites this paper
• Construction of Fluorescently-Tagged and Adenosine Nucleotide-Binding Mutations of the Human MutS Homolog Heterodimer MSH2-MSH3

  2009cites this paper
• MSH2 ATPase Domain Mutation Affects CTG•CAG Repeat Instability in Transgenic Mice

  2009cites this paper
• Mutations in the signature motif in MutS affect ATP‐induced clamp formation and mismatch repair

  2008cites this paper
• hMSH4-hMSH5 Adenosine Nucleotide Processing and Interactions with Homologous Recombination Machinery*

  2008cites this paper
• utagenic roles of DNA “ repair ” proteins in antibody iversity and disease-associated trinucleotide epeat instability

  2008cites this paper
• Mutagenic roles of DNA "repair" proteins in antibody diversity and disease-associated trinucleotide repeat instability.

  2008cites this paper
• Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease.

  2008cites this paper
• Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display distinct requirements for DNA binding domain I in mismatch recognition.

  2007cites this paper
• Signalisation moléculaire par le système de réparation des mésappariements de l'ADN et l'agent anticancéreux cisplatine : étude des interactions protéine MutS-composé de lésion du cisplatine

  2007cites this paper
• Saccharomyces cerevisiae Msh2-Msh3 Acts in Repair of Base-Base Mispairs

  2007cites this paper
• DNA repair systems as targets of cadmium toxicity.

  2006cites this paper
• DNA mismatch repair: functions and mechanisms.

  2006cites this paper
• Mismatch repair factor MSH2-MSH3 binds and alters the conformation of branched DNA structures predicted to form during genetic recombination.

  2006cites this paper
• CHAPTER 41 – Error-Prone Repair of Slipped (CTG)·(CAG) Repeats and Disease-Associated Expansions

  2006cites this paper
• Prokaryotic DNA mismatch repair.

  2006cites this paper
• (CAG)n-hairpin DNA binds to Msh2–Msh3 and changes properties of mismatch recognition

  2005cites this paper
• MSH2–MSH6 stimulates DNA polymerase η, suggesting a role for A:T mutations in antibody genes

  2005cites this paper
• Functional significance of minor MLH1 germline alterations found in colon cancer patients

  2005cites this paper
• Mechanism of DNA Mismatch Repair from Bacteria to Human

  2005cites this paper
• MSH2–MSH6 stimulates DNA polymerase (cid:1) , suggesting a role for A:T mutations in antibody genes

  2005cites this paper
• hMSH4-hMSH5 recognizes Holliday Junctions and forms a meiosis-specific sliding clamp that embraces homologous chromosomes.

  2004cites this paper
• ATP Increases the Affinity between MutS ATPase Domains

  2004cites this paper
• The mismatch repair complex hMutS alpha recognizes 5-fluorouracil-modified DNA: implications for chemosensitivity and resistance.

  2004cites this paper
• Bi-directional Processing of DNA Loops by Mismatch Repair-dependent and -independent Pathways in Human Cells*

  2003cites this paper
• A role for DNA mismatch repair in sensing and responding to fluoropyrimidine damage

  2003cites this paper
• The coordinated functions of the E. coli MutS and MutL proteins in mismatch repair.

  2003cites this paper
• Transfer of the MSH2·MSH6 Complex from Proliferating Cell Nuclear Antigen to Mispaired Bases in DNA*

  2003cites this paper
• Defining the function of XPC protein in psoralen and cisplatin-mediated DNA repair and mutagenesis.

  2003cites this paper
• DNA mismatch repair and cancer.

  2003cites this paper
• HNPCC mutations in hMSH2 result in reduced hMSH2-hMSH6 molecular switch functions.

  2002cites this paper
• Activation of Human MutS Homologs by 8-Oxo-guanine DNA Damage*

  2002cites this paper
• Human MutY Homolog, a DNA Glycosylase Involved in Base Excision Repair, Physically and Functionally Interacts with Mismatch Repair Proteins Human MutS Homolog 2/Human MutS Homolog 6*

  2002cites this paper
• hMutSβ Is Required for the Recognition and Uncoupling of Psoralen Interstrand Cross-Links In Vitro

  2002cites this paper
• Dominant Saccharomyces cerevisiae msh6 Mutations Cause Increased Mispair Binding and Decreased Dissociation from Mispairs by Msh2-Msh6 in the Presence of ATP*

  2002cites this paper
• IDENTIFICATION AND CHARACTERIZATION OF MULTIPLE DNA LOOP REPAIR PATHWAYS IN HUMAN CELLS

  2002cites this paper
• Intrachromosomal genomic instability in human sporadic colorectal cancer measured by genome-wide allelotyping and inter-(simple sequence repeat) PCR.

  2001cites this paper
• Composite active site of an ABC ATPase: MutS uses ATP to verify mismatch recognition and authorize DNA repair.

  2001cites this paper
• Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1

  2001cites this paper
• The Interaction of DNA Mismatch Repair Proteins with Human Exonuclease I*

  2001cites this paper
• Direct observation of three conformations of MutS protein regulated by adenine nucleotides.

  2001cites this paper