{
  "abstract": "DNA replication licensing is tightly coordinated with cell-cycle progression to ensure genome stability. Here we demonstrate that CIZ1, a nuclear matrix scaffold protein in human cells, coordinates DNA replication licensing through direct interactions with the Origin Recognition Complex (ORC), CDC6, and Cyclins E/A-CDK2. The C-terminal zinc finger region of CIZ1 mediates binding to the cyclin-binding motifs of ORC1 and CDC6, and Cyclin -CDK-dependent phosphorylation regulates these interactions. Cell cycle analyses demonstrated a dynamic association of CIZ1 with ORC1 and CDC6. Functional studies showed that CIZ1 depletion impaired MCM loading, reduced DNA synthesis, delayed S-phase progression and inhibited cell proliferation. Cancer cells overexpressing CIZ1 exhibited an enhanced dependency on its expression, and CRISPR tiling screens identified the C-terminal regulatory region containing cyclin-binding motifs and CDK phosphorylation sites as essential for cell proliferation. Acute degradation of CIZ1 further revealed an unexpected role in maintaining CCCTC-binding factor (CTCF) occupancy at specific genomic loci and regulating transcriptional programs associated with cell adhesion and migration, indicating that CIZ1 links DNA replication with higher-order genome organization. Finally, depletion of CIZ1 significantly suppressed colorectal tumor growth in xenograft models. Together, these findings establish CIZ1 as a multifunctional scaffold that integrates DNA replication licensing, Cyclin -CDK signaling, and chromatin architecture.",
  "abstract_shown": true,
  "affiliations": [
    "Cold Spring Harbor Laboratory"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "M. Hossain"
    },
    {
      "name": "M. Tramantano"
    },
    {
      "name": "S. Naik"
    },
    {
      "affs": [
        0
      ],
      "name": "B. Stillman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4a12753cqe2rm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.10.758243",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758243v1.full",
  "id": "4a12753cqe2rm",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758243v1",
  "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",
      "2730|Cancer-related Molecular Pathways"
    ]
  ],
  "openalex": "W7221659539",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758243v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4a12753cqe2rm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:33Z",
      "native_id": "10.64898/2026.10.10.758243",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758243v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A role for CIZ1, a Nuclear Matrix Protein Overexpressed in Cancer Cells, in Controlling the Initiation of DNA Replication",
  "title_text": "A role for CIZ1, a Nuclear Matrix Protein Overexpressed in Cancer Cells, in Controlling the Initiation of DNA Replication",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:33Z",
  "url": "https://research.draconitic.com/paper/4a12753cqe2rm",
  "venue": "bioRxiv",
  "versions": []
}