MSH6 mismatch repair ATPase MSH6 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: MSH6
Official Full Name: mismatch repair ATPase MSH6
Primary source: SGD:S000002504
Locus tag: YDR097C
See related: AllianceGenome:SGD:S000002504; FungiDB:YDR097C; VEuPathDB:YDR097C
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: PMS3; PMS6
Summary: Enables ATP binding activity; ATP hydrolysis activity; and four-way junction DNA binding activity. Contributes to guanine/thymine mispair binding activity and single base insertion or deletion binding activity. Involved in interstrand cross-link repair; meiotic mismatch repair; and replication fork arrest. Located in cytoplasm and nucleus. Part of MutSalpha complex. Used to study breast cancer; cancer (multiple); mismatch repair cancer syndrome; and ovarian disease (multiple). Human ortholog(s) of this gene implicated in Lynch syndrome; colorectal carcinoma; endometrial cancer; hereditary nonpolyposis colorectal cancer type 5; and mismatch repair cancer syndrome. Orthologous to human MSH6 (mutS homolog 6). [provided by Alliance of Genome Resources, Dec 2024]
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Genomic context

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See MSH6 in Genome Data Viewer

Location:: chromosome: IV

Exon count:: 1

Sequence:: Chromosome: IV; NC_001136.10 (640109..643837, complement)

Chromosome IV - NC_001136.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001136.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MutSalpha deficiency increases tolerance to DNA damage in yeast lacking postreplication repair.
Title: MutSα deficiency increases tolerance to DNA damage in yeast lacking postreplication repair.
Msh2-Msh6 Recognizes Mismatched DNA Base Pairs with Different Affinities. Msh2-Msh6 Binding Affects Mismatched Base Pair Dynamics.
Title: Mismatch Recognition by Saccharomyces cerevisiae Msh2-Msh6: Role of Structure and Dynamics.
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.
The mutant Msh2-Msh6 complexes exhibited normal mispair recognition and were proficient at recruiting the MMR endonuclease Mlh1-Pms1 to mispaired DNA.
Title: The properties of Msh2-Msh6 ATP binding mutants suggest a signal amplification mechanism in DNA mismatch repair.
MSH6 overexpression affected the integrity of the DNA replication fork, causing genome instability phenotypes.
Title: Genomic Instability Promoted by Overexpression of Mismatch Repair Factors in Yeast: A Model for Understanding Cancer Progression.
Msh2-Msh6 slides without hopping and is largely blocked by protein roadblocks.
Title: Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions.
Msh2-Msh6 localizes PCNA to repair sites after mispair recognition.
Title: PCNA and Msh2-Msh6 activate an Mlh1-Pms1 endonuclease pathway required for Exo1-independent mismatch repair.
analysis of the interaction between the Msh2 and Msh6 nucleotide-binding sites in the Saccharomyces cerevisiae Msh2-Msh6 complex
Title: Interaction between the Msh2 and Msh6 nucleotide-binding sites in the Saccharomyces cerevisiae Msh2-Msh6 complex.
results suggest that MSH2-MSH6 binding to homoduplex regions of DNA recruits NHP6A, which then prevents further binding of MSH2-MSH6 to these sites unless a mismatch is present.
Title: Modulation of the DNA-binding activity of Saccharomyces cerevisiae MSH2-MSH6 complex by the high-mobility group protein NHP6A, in vitro.
Interactions between Msh2-Msh6 and DNA are dominated by lateral movement of the protein along the helical axis and have implications for how MutS family members travel along DNA at different stages of the mismatch repair reaction.
Title: Dynamic basis for one-dimensional DNA scanning by the mismatch repair complex Msh2-Msh6.

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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	IDA Inferred from Direct Assay more info	PubMed
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP-dependent DNA damage sensor activity	IEA Inferred from Electronic Annotation more info
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables four-way junction DNA binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to guanine/thymine mispair binding	IDA Inferred from Direct Assay more info	PubMed
enables mismatched DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables mismatched DNA binding	IEA Inferred from Electronic Annotation more info
contributes_to single base insertion or deletion binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to single base insertion or deletion binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IEA Inferred from Electronic Annotation more info
involved_in DNA metabolic process	IEA Inferred from Electronic Annotation more info
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in interstrand cross-link repair	IGI Inferred from Genetic Interaction 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	IDA Inferred from Direct Assay more info	PubMed
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 replication fork arrest	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of MutSalpha complex	IBA Inferred from Biological aspect of Ancestor more info
part_of MutSalpha complex	IPI Inferred from Physical Interaction more info	PubMed
located_in cytoplasm	HDA more info	PubMed
located_in nucleus	HDA more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: mismatch repair ATPase MSH6

NP_010382.3

Protein required for mismatch repair in mitosis and meiosis; forms a complex with Msh2p to repair both single-base & insertion-deletion mispairs; also involved in interstrand cross-link repair; potentially phosphorylated by Cdc28p; contains PIP motif that binds PCNA (Pol30p) and Rev1p

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_001136.10 Reference assembly

Range

640109..643837 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001180405.3 → NP_010382.3 TPA: mismatch repair ATPase MSH6 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_010382.3

Status: REVIEWED

UniProtKB/Swiss-Prot

D6VS82, Q03834

UniProtKB/TrEMBL

C7GVP1

Conserved Domains (2) summary

COG0249
Location:306 → 1235

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

PRK08581
Location:71 → 282

PRK08581; amidase domain-containing protein