MLH3 mismatch repair protein MLH3 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: MLH3
Official Full Name: mismatch repair protein MLH3
Primary source: SGD:S000006085
Locus tag: YPL164C
See related: AllianceGenome:SGD:S000006085; FungiDB:YPL164C; VEuPathDB:YPL164C
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Summary: Predicted to enable ATP hydrolysis activity. Involved in meiotic mismatch repair and reciprocal meiotic recombination. Located in nucleus. Part of MutLgamma complex. Used to study hereditary nonpolyposis colorectal cancer type 7. Human ortholog(s) of this gene implicated in Lynch syndrome; colorectal cancer; endometrial cancer; and hereditary nonpolyposis colorectal cancer type 7. Orthologous to human MLH3 (mutL homolog 3). [provided by Alliance of Genome Resources, Oct 2024]
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Genomic context

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See MLH3 in Genome Data Viewer

Location:: chromosome: XVI

Exon count:: 1

Sequence:: Chromosome: XVI; NC_001148.4 (239350..241497, complement)

Chromosome XVI - NC_001148.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001148.4

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease.
Title: The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease.
Experimental exchange of paralogous domains in the MLH family provides evidence of sub-functionalization after gene duplication.
Title: Experimental exchange of paralogous domains in the MLH family provides evidence of sub-functionalization after gene duplication.
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.
mlh3Delta showed approximately 30% genome-wide reduction in crossovers and loss of the obligate crossover, but nonexchange chromosomes were efficiently segregated.
Title: Modulating Crossover Frequency and Interference for Obligate Crossovers in Saccharomyces cerevisiae Meiosis.
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.
observations support a direct role for an Mlh1-Mlh3 endonuclease activity in resolving recombination intermediates and in DNA mismatch repair.
Title: Mlh1-Mlh3, a meiotic crossover and DNA mismatch repair factor, is a Msh2-Msh3-stimulated endonuclease.
Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form.
Title: The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions.
Genetic analysis of mlh3 mutations reveals interactions between crossover promoting factors during meiosis in baker's yeast.
Title: Genetic analysis of mlh3 mutations reveals interactions between crossover promoting factors during meiosis in baker's yeast.
Overexpression of the mlh3-D523N mutant allele conferred a dominant-negative phenotype with respect to mismatch repair.
Title: A mutation in the putative MLH3 endonuclease domain confers a defect in both mismatch repair and meiosis in Saccharomyces cerevisiae.

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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 hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	ISS Inferred from Sequence or Structural Similarity 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 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 MutLgamma complex	IPI Inferred from Physical Interaction more info	PubMed
part_of mismatch repair complex	IBA Inferred from Biological aspect of Ancestor more info
part_of mismatch repair complex	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: mismatch repair protein MLH3

NP_015161.1

Protein involved in DNA mismatch repair and meiotic recombination; involved in crossing-over during meiotic recombination; forms a complex with Mlh1p; mammalian homolog is implicated mammalian microsatellite instability

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_001148.4 Reference assembly

Range

239350..241497 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001183978.1 → NP_015161.1 TPA: mismatch repair protein MLH3 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_015161.1

Status: REVIEWED

UniProtKB/Swiss-Prot

D6W3K4, Q12083

UniProtKB/TrEMBL

B3LKR3, C7GJB6, N1NW07

Conserved Domains (1) summary

COG0323
Location:1 → 715

MutL; DNA mismatch repair ATPase MutL [Replication, recombination and repair]