{
  "abstract": "RAD52 and CHK1 are critical factors that play pleiotropic roles in the DNA damage response (DDR), including the resolution of transcription–replication conflicts (TRCs). However, how their functions are modulated remains incomplete. Here, we reveal that the cleavage and polyadenylation specificity factor subunit 6 (CPSF6) is an unexpected DDR factor that enhances RAD52 stability and CHK1 activation. Specifically, CPSF6 competitively interacts with RAD52, thereby preventing RAD52 from interacting with the E3 ubiquitin ligase UHRF1 and subsequent proteasomal degradation. In addition, CPSF6 enhances the ATR–CHK1 interaction to promote CHK1 activation, thereby facilitating the activation of downstream CHK1–PLK1–RAD51 pathway. The dual functions of CPSF6 in RAD52 stabilization and CHK1 activation contribute to its role in TRC resolution. CPSF6 depletion causes R-loop accumulation and transcription-associated DNA damage. Notably, these roles of CPSF6 in the DDR are independent of its canonical role in pre-mRNA 3′-end processing. Collectively, our findings establish that CPSF6 is a novel factor critical for maintaining genomic stability, with the resolution of TRCs as an important mechanism.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 ,",
    "Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101 ,",
    "University of Chinese Academy of Sciences , Beijing 100049 ,",
    "China National Center for Bioinformation , Beijing 100101 ,",
    "Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing 100101 ,",
    "Nanjing Maternal and Child Health Institute, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital , Nanjing 210004 ,"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Honglin Wu",
      "orcid": "0000-0002-1175-5201"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Hui Fu",
      "orcid": "0009-0004-3125-246X"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Zhenzhen Fan"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Junying Qin"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Yifei Gong",
      "orcid": "0009-0003-5233-9081"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Hui Zheng"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Ruiyuan An"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Xiuxiu Miao",
      "orcid": "0009-0001-2534-5924"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Tie-Shan Tang",
      "orcid": "0000-0001-8975-6338"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Caixia Guo",
      "orcid": "0000-0002-2820-705X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/71vcfv9mkpv5e.bib",
  "cited_by": 0,
  "doi": "10.1093/nar/gkag1011",
  "fulltext_url": null,
  "id": "71vcfv9mkpv5e",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1011/8986611",
  "language": null,
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7223355779",
  "pdf_url": "https://academic.oup.com/nar/article-pdf/54/19/gkag1011/72410756/gkag1011.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/71vcfv9mkpv5e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:50Z",
      "native_id": "10.1093/nar/gkag1011",
      "source": "crossref",
      "url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1011/8986611"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA Repair Mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "CPSF6 maintains genomic stability by stabilizing RAD52 and promoting CHK1 activation",
  "title_text": "CPSF6 maintains genomic stability by stabilizing RAD52 and promoting CHK1 activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:50Z",
  "url": "https://research.draconitic.com/paper/71vcfv9mkpv5e",
  "venue": "Nucleic Acids Research",
  "versions": []
}