MLH1 mismatch repair ATPase MLH1 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Gene symbol: MLH1
Gene description: mismatch repair ATPase MLH1
Primary source: SGD:S000004777
Locus tag: YMR167W
See related: AllianceGenome:SGD:S000004777
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Also known as: PMS2
Summary: Enables ATP binding activity and ATP hydrolysis activity. Contributes to DNA binding activity. Involved in meiotic heteroduplex formation; meiotic mismatch repair; and reciprocal meiotic recombination. Located in mitochondrion and nucleus. Part of MutLalpha complex; MutLbeta complex; and MutLgamma complex. Used to study colorectal cancer. Human ortholog(s) of this gene implicated in Lynch syndrome (multiple); gastrointestinal system cancer (multiple); lung cancer; mismatch repair cancer syndrome; and sporadic breast cancer. Orthologous to human MLH1 (mutL homolog 1). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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Location:: chromosome: XIII

Exon count:: 1

Sequence:: Chromosome: XIII; NC_001145.3 (594886..597195)

Chromosome XIII - NC_001145.3 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001145.3

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The unstructured linker of Mlh1 contains a motif required for endonuclease function which is mutated in cancers.
Title: The unstructured linker of Mlh1 contains a motif required for endonuclease function which is mutated in cancers.
Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation.
Title: Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation.
Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair.
Title: Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair.
Results provide evidence that the MLH1 gene encoding one of the crucial components of the mismatch repair, is required for transcriptional repression at silent mating-type loci and telomeres.
Title: Yeast mismatch repair components are required for stable inheritance of gene silencing.
Experiments were performed in an MMR-proficient strain, a strain with compromised mismatch-recognition activity (msh6Delta) and a strain that retained mismatch-recognition activity but was unable to process mismatches (mlh1Delta).
Title: Mismatch recognition and subsequent processing have distinct effects on mitotic recombination intermediates and outcomes in yeast.
Mlh1-Pms1 complexes with shorter IDRs that disrupt MMR retain wild-type DNA binding affinity but are impaired for diffusion on both naked and nucleosome-coated DNA. Moreover, the IDRs also regulate the adenosine triphosphate hydrolysis and nuclease activities that are encoded in the structured N- and C-terminal domains of the complex
Title: Intrinsically disordered regions regulate both catalytic and non-catalytic activities of the MutLα mismatch repair complex.
Genotyping analysis indicated that MLH1-PMS1 incompatibility was the major driver of mutation rate in the isolates. The variation in the mutation rate of incompatible spore clones could be due to background suppressors and enhancers, as well as aneuploidy seen in the spore clones.
Title: Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Baker's Yeast.
Here the authors show that the budding yeast mismatch repair related MutLbeta complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition.
Title: Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion.
Our observations provide a structure-function map for Mlh3 that reveals the importance of protein-protein interactions in regulating Mlh1-Mlh3's enzymatic activity. They also illustrate how defective meiotic components can alter the fate of meiotic recombination intermediates, providing new insights for how meiotic recombination pathways are regulated.
Title: mlh3 mutations in baker's yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide.
These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.
Title: Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

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Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ATP-dependent DNA damage sensor activity	IEA Inferred from Electronic Annotation more info
enables mismatched DNA binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in meiosis I cell cycle process	IEA Inferred from Electronic Annotation more info
involved_in meiotic heteroduplex formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in meiotic mismatch repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mismatch repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in mismatch repair	IEA Inferred from Electronic Annotation more info
involved_in mismatch repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in reciprocal meiotic recombination	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of MutLalpha complex	IBA Inferred from Biological aspect of Ancestor more info
part_of MutLalpha complex	IPI Inferred from Physical Interaction more info	PubMed
part_of MutLbeta complex	IPI Inferred from Physical Interaction more info	PubMed
part_of MutLgamma complex	IPI Inferred from Physical Interaction more info	PubMed
located_in cytoplasm	HDA more info	PubMed
part_of mismatch repair complex	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	HDA more info	PubMed
located_in nucleus	HDA more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: mismatch repair ATPase MLH1

NP_013890.1

Protein required for mismatch repair in mitosis and meiosis; also required for crossing over during meiosis; forms a complex with Pms1p and Msh2p-Msh3p during mismatch repair; required for silencing at the silent mating-type loci and telomeres; human homolog is associated with hereditary non-polyposis colon cancer