{
  "abstract": "The chromatin remodeler HELLS acts as a pleiotropic guardian of genomic integrity, orchestrating critical processes from DNA replication to DNA damage repair. In anaplastic large cell lymphoma (ALCL), HELLS functions as a transcriptional sentinel, fine-tuning chromatin accessibility and RNA polymerase II kinetics to sustain the oncogenic transcriptional landscape essential for lymphomagenesis. Here we show that HELLS preserves genomic stability and sustains ALK-negative ALCL proliferation by preventing transcription–replication conflicts. HELLS acts as a global regulator of R-loop homeostasis while transcriptionally sustaining MCM5, a core subunit of the replicative MCM2–7 complex, which locally restrains replication-transcription collisions at actively transcribed loci. Mechanistically, HELLS loss reduces MCM5 levels, triggering aberrant firing of origins within transcriptionally active regions and consequent collisions between replication forks and the transcription machinery. Being positioned distally from R-loop-enriched sites, HELLS and MCM5 cooperate to preserve genome integrity, with MCM5 acting as the effector that delivers locus-specific protection against replication-associated genomic instability. Pharmacological or genetic disruption of this axis increases R-loop burden and drastically reduces the survival of ALK-negative ALCL cells, providing a rationale for combination therapy. Collectively, the HELLS–MCM5 module emerges as a master coordinator of transcription–replication dynamics and a novel therapeutic vulnerability in aggressive lymphomas.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia , Viale Risorgimento 80, 42123 Reggio Emilia ,",
    "Clinical and Experimental Medicine PhD Programme, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia , Modena 41125 ,",
    "Molecular and Regenerative Medicine PhD Program, Department of Life Sciences, University of Modena and Reggio Emilia , Modena 41125 ,",
    "Pathology Unit, Department of Oncology, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia , Reggio Emilia 42123 ,",
    "Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia , Viale Umberto I 50, 42123 Reggio Emilia ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Selene Mallia"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Giulia Gambarelli"
    },
    {
      "affs": [
        0
      ],
      "name": "Emanuele Vitale",
      "orcid": "0000-0003-1866-2101"
    },
    {
      "affs": [
        0
      ],
      "name": "Veronica Manicardi"
    },
    {
      "affs": [
        0
      ],
      "name": "Elisa Salviato"
    },
    {
      "affs": [
        0
      ],
      "name": "Pierluigi Di Chiaro"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Rebecca Vezzani"
    },
    {
      "affs": [
        0
      ],
      "name": "Benedetta Donati"
    },
    {
      "affs": [
        0
      ],
      "name": "Federica Torricelli"
    },
    {
      "affs": [
        3
      ],
      "name": "Magda Zanelli"
    },
    {
      "affs": [
        0
      ],
      "name": "Annalisa Tameni"
    },
    {
      "affs": [
        3
      ],
      "name": "Ione Tamagnini"
    },
    {
      "affs": [
        0
      ],
      "name": "Noemi Puccio"
    },
    {
      "affs": [
        4
      ],
      "name": "Antonino Neri"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessia Ciarrocchi",
      "orcid": "0000-0002-5541-2075"
    },
    {
      "affs": [
        0
      ],
      "name": "Valentina Fragliasso",
      "orcid": "0000-0002-4189-0316"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/akas4zt9q14qm.bib",
  "cited_by": 0,
  "doi": "10.1093/nar/gkag1023",
  "fulltext_url": "https://europepmc.org/articles/PMC13720504",
  "id": "akas4zt9q14qm",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1023/9005088",
  "language": "eng",
  "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": [
    [
      "heading",
      "AcademicSubjects/SCI00010"
    ],
    [
      "heading",
      "Genome Integrity, Repair and Replication"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://academic.oup.com/nar/article-pdf/54/20/gkag1023/72614317/gkag1023.pdf",
  "pmcid": "PMC13720504",
  "pmid": "42960509",
  "published": "2026-10-01",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/akas4zt9q14qm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:50Z",
      "native_id": "10.1093/nar/gkag1023",
      "source": "crossref",
      "url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1023/9005088"
    },
    {
      "first_seen": "2026-11-01T00:20:52Z",
      "native_id": "MED:42960509",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42960509"
    },
    {
      "first_seen": "2026-11-03T12:21:22Z",
      "native_id": "PMC13720504",
      "source": "pmc",
      "url": "https://doi.org/10.1093/nar/gkag1023"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:0305-1048",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The HELLS–MCM5 axis coordinates transcription–replication dynamics to preserve genomic integrity in ALK-negative anaplastic large cell lymphoma",
  "title_text": "The HELLS–MCM5 axis coordinates transcription–replication dynamics to preserve genomic integrity in ALK-negative anaplastic large cell lymphoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:22Z",
  "url": "https://research.draconitic.com/paper/akas4zt9q14qm",
  "venue": "Nucleic Acids Research",
  "versions": []
}