{
  "abstract": "BRCA2 deficiency induces chronic replication stress, yet how human mammary epithelial cells adapt before malignant transformation remains poorly understood. Here, we identify polymerase iota (Pol ι) as a context-dependent regulator of replication stress responses in BRCA2-deficient mammary epithelium. Single-cell transcriptomic analysis of preneoplastic breast epithelium from BRCA2 mutation carriers revealed enrichment of POLI-positive hormone-sensing cells, while BRCA2 depletion increased nuclear Pol ι in mammary epithelial models. Functionally, Pol ι promoted post-S-phase DNA synthesis specifically in BRCA2-deficient cells. Unexpectedly, POLI depletion reduced chromosomal instability and replication stress markers, while enhancing replication fork progression under replication stress. POLI depletion was also associated with expansion of a luminal-like epithelial population, linking altered replication stress processing to epithelial cell state remodeling. These findings identify Pol ι as a regulator of replication stress adaptation and provide a framework for understanding early cellular changes preceding BRCA2-associated breast tumorigenesis.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "Kavya Vipparthi",
      "orcid": "0000-0002-5656-3166"
    },
    {
      "name": "Ariana Bellare"
    },
    {
      "name": "Resul Ozbilgic",
      "orcid": "0000-0002-5275-5355"
    },
    {
      "name": "Peter Bazeley",
      "orcid": "0000-0002-6272-5686"
    },
    {
      "name": "Nishtha Khanna"
    },
    {
      "name": "Fangfang Wang"
    },
    {
      "name": "Anand Bhushan",
      "orcid": "0000-0002-0966-0289"
    },
    {
      "name": "Liangqi Xie"
    },
    {
      "name": "Zahraa Al-Hilli"
    },
    {
      "name": "You-Wei Zhang"
    },
    {
      "name": "Mihriban Karaayvaz",
      "orcid": "0000-0002-6264-2477"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7688pdbkj8ttg.bib",
  "cited_by": 0,
  "doi": "10.1016/j.isci.2026.117830",
  "fulltext_url": "https://europepmc.org/articles/PMC13677199",
  "id": "7688pdbkj8ttg",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03211-6",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Molecular biology"
    ],
    [
      "heading",
      "cancer"
    ],
    [
      "heading",
      "cell biology"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7221162337",
  "pdf_url": "https://europepmc.org/articles/PMC13677199?pdf=render",
  "pmcid": "PMC13677199",
  "pmid": "42894850",
  "published": "2026-10-09",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/7688pdbkj8ttg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:16Z",
      "native_id": "10.1016/j.isci.2026.117830",
      "source": "feed-cell",
      "url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03211-6"
    },
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1016/j.isci.2026.117830",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2589004226032116"
    },
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42894850",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894850"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Molecular biology",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "heading:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "heading:cancer",
      "subfield": "oncology"
    }
  ],
  "title": "Polymerase iota coordinates adaptation to replication stress in BRCA2-deficient mammary epithelial cells",
  "title_text": "Polymerase iota coordinates adaptation to replication stress in BRCA2-deficient mammary epithelial cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/7688pdbkj8ttg",
  "venue": "iScience",
  "versions": []
}