{
  "abstract": "Eukaryotic DNA replication relies on organized spatial-temporal domains, yet how neighboring origins are coordinated at the single-molecule level remains unresolved. Combining single-molecule DNA combing with super-resolution microscopy, we demonstrate that during unperturbed early S-phase, adjacent replication origins across diverse vertebrate species fire synchronously as a coordinated unit. This domain-wide temporal harmony is continuously enforced by a baseline, constitutive ATR CHK1 signaling axis that restrains local CDK2 and CDC7 kinase activities. Strikingly, replication stress dismantles this coordination, shifting origin activation toward an asynchronous, replicon-autonomous mode. Mechanistically, stress-induced phosphorylation of the cohesin subunit SMC1A promotes an SMC1A ATR complex that sequesters ATR at stalled replication forks. This localized sequestration creates a regional ATR loss-of-function phenotype, relieving CDK2/CDC7 suppression and driving premature, uncoordinated origin firing. Super-resolution imaging shows that ATR sequestration structurally reorganizes replication foci, converting coordinated clustered foci into fragmented, lower-density clusters. Together, our findings uncover a baseline role for constitutive ATR signaling in enforcing domain synchrony and reveal a molecular switch that dynamically decouples origin activation during genomic stress to safeguard chromosome duplication.",
  "abstract_shown": true,
  "affiliations": [
    "Hebrew University of Jerusalem"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "J. Kamar"
    },
    {
      "name": "S. Eden"
    },
    {
      "name": "S. K. Pradhan"
    },
    {
      "name": "M. K. Pabba"
    },
    {
      "name": "M. Arroyo"
    },
    {
      "name": "A. Greenberg"
    },
    {
      "name": "L. Daniel"
    },
    {
      "name": "M. C. Cardoso"
    },
    {
      "affs": [
        0
      ],
      "name": "I. Simon"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ffd8tsvsxy7pb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.19.760027",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760027v1.full",
  "id": "ffd8tsvsxy7pb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760027v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7223036568",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760027v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ffd8tsvsxy7pb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:45Z",
      "native_id": "10.64898/2026.10.19.760027",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760027v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Constitutive ATR Signaling Enforces Domain-Wide Origin Synchrony",
  "title_text": "Constitutive ATR Signaling Enforces Domain-Wide Origin Synchrony",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:45Z",
  "url": "https://research.draconitic.com/paper/ffd8tsvsxy7pb",
  "venue": "bioRxiv",
  "versions": []
}