PubMed:24443562 JSONTXT

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Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions.\nMutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":118},"obj":"Sentence"},{"id":"T2","span":{"begin":119,"end":240},"obj":"Sentence"},{"id":"T3","span":{"begin":241,"end":503},"obj":"Sentence"},{"id":"T4","span":{"begin":504,"end":713},"obj":"Sentence"},{"id":"T5","span":{"begin":714,"end":802},"obj":"Sentence"},{"id":"T6","span":{"begin":803,"end":879},"obj":"Sentence"},{"id":"T7","span":{"begin":880,"end":990},"obj":"Sentence"},{"id":"T8","span":{"begin":991,"end":1148},"obj":"Sentence"},{"id":"T9","span":{"begin":1149,"end":1239},"obj":"Sentence"},{"id":"T10","span":{"begin":1240,"end":1332},"obj":"Sentence"},{"id":"T11","span":{"begin":1333,"end":1482},"obj":"Sentence"},{"id":"T12","span":{"begin":1483,"end":1608},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions.\nMutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":4,"end":28},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":1013,"end":1018},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"NCBItxid:4932"},{"id":"A2","pred":"db_id","subj":"T2","obj":"NCBItxid:9606"}],"text":"The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions.\nMutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis."}

{"project":"GlyCosmos6-CLO","denotations":[{"id":"T1","span":{"begin":29,"end":33},"obj":"http://purl.obolibrary.org/obo/CLO_0007748"},{"id":"T2","span":{"begin":163,"end":167},"obj":"http://purl.obolibrary.org/obo/CLO_0007748"},{"id":"T3","span":{"begin":387,"end":395},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T4","span":{"begin":399,"end":403},"obj":"http://purl.obolibrary.org/obo/CLO_0007748"},{"id":"T5","span":{"begin":540,"end":544},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T6","span":{"begin":571,"end":575},"obj":"http://purl.obolibrary.org/obo/CLO_0007748"},{"id":"T7","span":{"begin":697,"end":712},"obj":"http://purl.obolibrary.org/obo/GO_0043234"},{"id":"T8","span":{"begin":742,"end":746},"obj":"http://purl.obolibrary.org/obo/CLO_0007748"},{"id":"T9","span":{"begin":1019,"end":1023},"obj":"http://purl.obolibrary.org/obo/CLO_0007748"},{"id":"T10","span":{"begin":1414,"end":1418},"obj":"http://purl.obolibrary.org/obo/CLO_0007748"}],"text":"The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions.\nMutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis."}

{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":118},"obj":"DRI_Approach"},{"id":"T2","span":{"begin":119,"end":240},"obj":"DRI_Challenge"},{"id":"T3","span":{"begin":241,"end":503},"obj":"DRI_Challenge"},{"id":"T4","span":{"begin":504,"end":713},"obj":"DRI_Background"},{"id":"T5","span":{"begin":714,"end":802},"obj":"DRI_Approach"},{"id":"T6","span":{"begin":803,"end":879},"obj":"DRI_Approach"},{"id":"T7","span":{"begin":880,"end":990},"obj":"DRI_Approach"},{"id":"T8","span":{"begin":991,"end":1148},"obj":"DRI_Outcome"},{"id":"T9","span":{"begin":1149,"end":1239},"obj":"DRI_Outcome"},{"id":"T10","span":{"begin":1240,"end":1332},"obj":"DRI_Approach"},{"id":"T11","span":{"begin":1333,"end":1482},"obj":"DRI_Outcome"},{"id":"T12","span":{"begin":1483,"end":1608},"obj":"DRI_Approach"}],"text":"The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions.\nMutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis."}