Fmp45 promotes Rad53 dephosphorylation via Ptc2 interaction to attenuate checkpoint signaling and maintain genome stability.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41386832", "kind": "science-record", "revision": 1, "content_hash": "sha256:25a8d3253e5b19006e4b2babc515a6211970face0ba1736ed51226f1c10d435f", "created_at": "2026-11-01T20:31:23Z", "updated_at": "2026-11-01T20:31:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Fmp45 promotes Rad53 dephosphorylation via Ptc2 interaction to attenuate checkpoint signaling and maintain genome stability.", "doi": "10.1016/j.jgeb.2025.100567", "pmid": "41386832", "authors": ["Zhongyi Cong", "Jingyuan Jiang", "Mengyuan Li", "Chenqi Yan", "Jiayin Li", "Xinmin Zhang"], "journal": "Journal, genetic engineering & biotechnology", "year": 2025, "abstract": "BACKGROUND: Double-strand breaks (DSBs) are repaired through the coordinated action of DNA damage checkpoint pathways, homologous recombination (HR), and non-homologous end joining (NHEJ) mechanisms. Given the complexity of DSB repair networks, the identification of novel regulatory factors remains essential for a comprehensive understanding of genomic stability maintenance. Fmp45, a membrane protein previously implicated in salt stress response but with no known role in DNA repair, was found to be upregulated in multiple DNA damage-related transcriptomic datasets (GEO: GSE83454, GSE155701, GSE74642). This observation led us to hypothesize that Fmp45 might represent a previously unrecognized component of the DSB repair machinery. In this study, we demonstrate that Fmp45 functions as a zeocin-specific modulator of the DSB response in Saccharomyces cerevisiae.\nMETHODS: Growth phenotypes were analysed to investigate FMP45 deletion (fmp45Δ) and its genetic interactions with other genes, protein expression and Rad53 phosphorylation was assessed by Western blotting, protein localization was analysed by Laser confocal microscopy, cell cycle progression was determined by flow cytometry, and protein-protein interactions was probed yeast two-hybrid assays.\nRESULTS: Growth assays revealed that fmp45Δ mutants exhibited hypersensitivity to DSBs induced by zeocin but not to other DNA lesions caused by hydroxyurea, methyl methanesulfonate, 4-nitroquinoline-1-oxide, or camptothecin. Genetic interaction analysis showed that Fmp45 cooperated with checkpoint gene Rad9 but not with HR-related genes (Sae2, Exo1) or NHEJ factor yku70. Laser confocal microscopy confirmed that FMP45 deletion did not impair nuclear localization of Rad51, a key mediator of HR-mediated DNA strand invasion. Further analysis of Rad53 phosphorylation/dephosphorylation dynamics, growth phenotypes of fmp45Δ with phosphatase (ptc2Δ, pph3Δ) and checkpoint effector (rad9Δ, mrc1Δ) mutants, cell cycle profiling, and yeast two-hybrid assays demonstrated that Fmp45 interacts with Ptc2 to promote Rad53 dephosphorylation, thereby preventing excessive cell cycle arrest.\nCONCLUSION: These findings elucidate a critical checkpoint-phosphatase coordination mechanism ensuring timely DNA damage recovery and genomic stability, identifying Fmp45 as a key regulator balancing DNA repair fidelity with cell cycle resumption following DSBs.", "claims": [{"id": "claim-data-access", "statement": "Three yeast DNA damage-related datasets, GSE83454 (HU), GSE155701 (MMS) and GSE74642 (4-nitroquinoline-1-oxide [4-NQO]), were retrieved from the Gene Expression Omnibus (GEO) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41386832", "locator": "sections[9] \"Fmp45 is involved in the DNA damage caused by genotoxin zeocin.\" paragraph 2", "quote": "Three yeast DNA damage-related datasets, GSE83454 (HU), GSE155701 (MMS) and GSE74642 (4-nitroquinoline-1-oxide [4-NQO]), were retrieved from the Gene Expression Omnibus (GEO) database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Fmp45 is a zeocin-specific modulator of the double-strand-break response that interacts with Ptc2 to promote Rad53 dephosphorylation and prevent excessive cell-cycle arrest.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41386832", "locator": "sections[0] \"Abstract\" paragraph 6", "quote": "In this study, we demonstrate that Fmp45 functions as a zeocin-specific modulator of the DSB response in Saccharomyces cerevisiae."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Fmp45 is a zeocin-specific modulator of the double-strand-break response that interacts with Ptc2 to promote Rad53 dephosphorylation and prevent excessive cell-cycle arrest.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41386832"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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