{
  "abstract": "Cells entering mitosis with incompletely replicated DNA face catastrophic chromosome segregation failure. During interphase, the replisome-associated E3 ubiquitin ligase TRAIP ubiquitylates barriers in front of the fork to allow replisome progression. In mitosis, TRAIP is reprogrammed from a trans-acting to a cis-acting ligase that can ubiquitylate the replisome itself. This enables the processing of unreplicated DNA by promoting replisome disassembly, fork breakage, and joining of the broken chromosome arms. Here, we describe a mechanism for this reprogramming: The adenosine triphosphatase transcription termination factor 2 (TTF2) is recruited to the replisome, where its noncatalytic N-terminal domain tethers cyclin B-cyclin-dependent kinase 1-phosphorylated TRAIP to the leading strand DNA polymerase ε in a geometry that allows replisome ubiquitylation. Thus, a phosphoregulated architectural switch alters replisome organization in mitosis to safeguard genome integrity before chromosome segregation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA",
    "Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA",
    "Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Boston Children’s Hospital, Boston, MA 02215, USA",
    "Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA",
    "Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA",
    "Generate:Biomedicines, Boston, MA, USA",
    "Arrakis Therapeutics, Waltham, MA, USA",
    "Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA",
    "Present Address: Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO 63110, USA",
    "Molecular Genetics, Department of Biology, RPTU University Kaiserslautern-Landau, Kaiserslautern, Germany",
    "Howard Hughes Medical Institute"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Geylani Can",
      "orcid": "0000-0002-1716-7830"
    },
    {
      "affs": [
        0
      ],
      "name": "Maksym Shyian",
      "orcid": "0000-0003-4845-2332"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Archana Krishnamoorthy",
      "orcid": "0000-0002-3305-6612"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Samreen Ahmed",
      "orcid": "0009-0005-6573-4034"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Yang Lim",
      "orcid": "0000-0001-6880-8418"
    },
    {
      "affs": [
        6,
        0
      ],
      "name": "Alex Wu"
    },
    {
      "affs": [
        7
      ],
      "name": "Raphael Pavani",
      "orcid": "0000-0002-7187-2995"
    },
    {
      "affs": [
        0,
        8
      ],
      "name": "Manal S. Zaher",
      "orcid": "0000-0002-7785-4384"
    },
    {
      "affs": [
        7
      ],
      "name": "André Nussenzweig",
      "orcid": "0000-0002-8952-7268"
    },
    {
      "affs": [
        9
      ],
      "name": "Markus Räschle",
      "orcid": "0000-0002-6737-7203"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Thomas E. Wilson",
      "orcid": "0000-0002-8345-4985"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Thomas W. Glover",
      "orcid": "0000-0003-4408-515X"
    },
    {
      "affs": [
        0,
        10
      ],
      "name": "Johannes C. Walter",
      "orcid": "0000-0002-4186-7570"
    },
    {
      "affs": [
        1,
        2,
        10
      ],
      "name": "David S. Pellman",
      "orcid": "0000-0001-5306-8031"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d9d9253w70a64.bib",
  "cited_by": 13,
  "doi": "10.1126/science.aeh1834",
  "fulltext_url": null,
  "id": "d9d9253w70a64",
  "issns": [
    "0036-8075",
    "0193-4511",
    "1095-9203"
  ],
  "landing_url": "https://doi.org/10.1126/science.aeh1834",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7167098178",
  "pdf_url": null,
  "pmcid": "PMC11623681",
  "pmid": "39651145",
  "published": "2026-07-02",
  "publisher": "American Association for the Advancement of Science",
  "ris": "https://research.draconitic.com/paper/d9d9253w70a64.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W7167098178",
      "source": "openalex",
      "url": "https://doi.org/10.1126/science.aeh1834"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA Repair Mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A CDK1 phospho-switch reprograms TRAIP to unload replisomes in mitosis",
  "title_text": "A CDK1 phospho-switch reprograms TRAIP to unload replisomes in mitosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:41Z",
  "url": "https://research.draconitic.com/paper/d9d9253w70a64",
  "venue": "Science",
  "versions": []
}