{
  "abstract": "R-loops are three-stranded nucleic acid structures formed primarily during transcription that can obstruct replication fork progression, leading to replication stress and genome instability. Although RNA helicases are increasingly implicated in R-loop metabolism, how individual helicases safeguard genome integrity remains incompletely understood. Here we identify DHX30, a neurodevelopmental disorder-associated DExH-box RNA helicase, as a replication stress-responsive regulator of R-loops. We show that DHX30 localizes to the nucleus in addition to its known cytoplasmic and mitochondrial pools, and that its nuclear abundance in-creases following aphidicolin or camptothecin treatment. DHX30 deficiency results in RNA:DNA hybrid accumulation in human cells and zebrafish, R-loop-dependent DNA double-strand breaks, micronucleus formation, reduced DNA synthesis, and altered expression of immediate-early stress genes under basal conditions and following replication perturbation. Biochemically, DHX30 binds branched nucleic acid structures and directly unwinds R-loop substrates containing a 3' single-stranded RNA overhang in an ATP- and polarity-dependent manner. Proteomic analyses place DHX30 within a nuclear network of RNA- and R-loop-associated factors, including the RNA helicase DHX9. These findings establish DHX30 as a conserved R-loop-resolving helicase that protects from R-loop-induced replication perturbations, contributes to transcriptional homeostasis, and maintains genome stability, thereby providing a mechanistic framework for understanding DHX30-associated neurodevelopmental disorders.",
  "abstract_shown": true,
  "affiliations": [
    "University of Regensburg"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "E. R. Nedelcu"
    },
    {
      "name": "N. C. Yeo"
    },
    {
      "name": "H. Huber"
    },
    {
      "name": "A. B. Prusty"
    },
    {
      "name": "T. Q. Truong"
    },
    {
      "name": "N. D. P. Dang"
    },
    {
      "name": "S. Harder"
    },
    {
      "name": "J. Lederbauer"
    },
    {
      "affs": [
        0
      ],
      "name": "I. Lessel"
    },
    {
      "name": "N. Ripin"
    },
    {
      "name": "C. Kiel"
    },
    {
      "name": "U. Fischer"
    },
    {
      "name": "H.-J. Kreienkamp"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Lessel"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/859v9gjbxjt72.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.25.761626",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.761626v1.full",
  "id": "859v9gjbxjt72",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.761626v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7224021800",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.761626v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/859v9gjbxjt72.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:51Z",
      "native_id": "10.64898/2026.10.25.761626",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.25.761626v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "DHX30 is a replication stress-responsive R-loop helicase that safeguards genome stability",
  "title_text": "DHX30 is a replication stress-responsive R-loop helicase that safeguards genome stability",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:51Z",
  "url": "https://research.draconitic.com/paper/859v9gjbxjt72",
  "venue": "bioRxiv",
  "versions": []
}