Proteomic Analysis Reveals a Novel Mutator S (MutS) Partner Involved in Mismatch Repair Pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27037360", "kind": "science-record", "revision": 2, "content_hash": "sha256:3630f9c9c1b890502d2e4aecacad73d529b8dfafb610d8b2c60c8c7bbfa344ec", "created_at": "2026-11-01T15:40:17Z", "updated_at": "2026-11-01T18:48:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic Analysis Reveals a Novel Mutator S (MutS) Partner Involved in Mismatch Repair Pathway.", "doi": "10.1074/mcp.M115.056093", "pmid": "27037360", "authors": ["Zhen Chen", "Mykim Tran", "Mengfan Tang", "Wenqi Wang", "Zihua Gong", "Junjie Chen"], "journal": "Molecular & cellular proteomics : MCP", "year": 2016, "abstract": "The mismatch repair (MMR) family is a highly conserved group of proteins that function in correcting base-base and insertion-deletion mismatches generated during DNA replication. Disruption of this process results in characteristic microsatellite instability (MSI), repair defects, and susceptibility to cancer. However, a significant fraction of MSI-positive cancers express MMR genes at normal levels and do not carry detectable mutation in known MMR genes, suggesting that additional factors and/or mechanisms may exist to explain these MSI phenotypes in patients. To systematically investigate the MMR pathway, we conducted a proteomic analysis and identified MMR-associated protein complexes using tandem-affinity purification coupled with mass spectrometry (TAP-MS) method. The mass spectrometry data have been deposited to the ProteomeXchange with identifier PXD003014 and DOI 10.6019/PXD003014. We identified 230 high-confidence candidate interaction proteins (HCIPs). We subsequently focused on MSH2, an essential component of the MMR pathway and uncovered a novel MSH2-binding partner, WDHD1. We further demonstrated that WDHD1 forms a stable complex with MSH2 and MSH3 or MSH6,i.e.the MutS complexes. The specific MSH2/WDHD1 interaction is mediated by the second lever domain of MSH2 and Ala(1123)site of WDHD1. Moreover, we showed that, just like MSH2-deficient cells, depletion of WDHD1 also led to 6-thioguanine (6-TG) resistance, indicating that WDHD1 likely contributes to the MMR pathway. Taken together, our study uncovers new components involved in the MMR pathway, which provides candidate genes that may be responsible for the development of MSI-positive cancers.", "claims": [{"id": "claim-target-result", "statement": "The paper reports a proteomic TAP-MS analysis identifying 230 high-confidence candidate interaction proteins, with the mass-spectrometry data deposited in ProteomeXchange under identifier PXD003014 (DOI 10.6019/PXD003014). No statistical method is described in the provided text, and no numerical result is reported specifically for the registered statistical-method target.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:27037360", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The mass spectrometry data have been deposited to the ProteomeXchange with identifier PXD003014 and DOI 10.6019/PXD003014."}, {"asset": "source:pmid:27037360", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified 230 high-confidence candidate interaction proteins (HCIPs)."}, {"asset": "source:pmid:27037360", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Taken together, our study uncovers new components involved in the MMR pathway, which provides candidate genes that may be responsible for the development of MSI-positive cancers."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper reports a proteomic TAP-MS analysis identifying 230 high-confidence candidate interaction proteins, with the mass-spectrometry data deposited in ProteomeXchange under identifier PXD003014 (DOI 10.6019/PXD003014). 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