Evidence map›Paper›PMID 40304571›Full record

ArticleeLife2025

DNA replication in primary hepatocytes without the six-subunit ORC.

Róża K Przanowska, Yuechuan Chen, Takayuki-Okano Uchida, Etsuko Shibata, Xiaoxiao Hao, Isaac Segura Rueda, Kate Jensen, Piotr Przanowski, Anthony Trimboli, Yoshiyuki Shibata and 2 more

Abstract read
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Róża K Przanowska *Dept. of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United States.ORCID https://orcid.org/0000-0003-1278-6242
Yuechuan Chen *Dept. of Genetics, University of Alabama at Birmingham, Birmingham, United States.ORCID https://orcid.org/0000-0001-6856-1582
Takayuki-Okano UchidaCancer Center, University of Wisconsin in Milwaukee, Milwaukee, United States.
Etsuko ShibataDept. of Genetics, University of Alabama at Birmingham, Birmingham, United States.
Xiaoxiao HaoDept. of Genetics, University of Alabama at Birmingham, Birmingham, United States.ORCID https://orcid.org/0000-0003-4404-5246
Isaac Segura RuedaDept. of Genetics, University of Alabama at Birmingham, Birmingham, United States.
Kate JensenDept. of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United States.
Piotr PrzanowskiDept. of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United States.ORCID https://orcid.org/0000-0002-9191-4769
Anthony TrimboliCancer Center, University of Wisconsin in Milwaukee, Milwaukee, United States.
Yoshiyuki ShibataDept. of Genetics, University of Alabama at Birmingham, Birmingham, United States.
Gustavo LeoneCancer Center, University of Wisconsin in Milwaukee, Milwaukee, United States.
Anindya DuttaDept. of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, United States.ORCID https://orcid.org/0000-0002-4319-0073

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9M
Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Dina Gould Halme · 1987 to 2026
$72.1M
The role of MCM8-9 in genomic instability of cancersR01CA060499 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Anindya Dutta · 1994 to 2026
$8.6M
Long non-coding RNA Heterogeneity in ER + Breast CancerK00CA253732 · NCI · UNIVERSITY OF VIRGINIA · PI PRZANOWSKA, ROZA KAMILA · 2021 to 2024
$400k
Long non-coding RNAs as novel therapeutic targets in gliomas treatmentF99CA253732 · NCI · UNIVERSITY OF VIRGINIA · PI PRZANOWSKA, ROZA KAMILA · 2020 to 2020
$36k
Medical College of Wisconsin Advancing a Healthier Wisconsin EndowmentMedical College of Wisconsin the Dr. Glenn R. and Nancy A. Linnerson Endowed FundNCI NIH HHS F99 CA253732NCI NIH HHS F99/K00CA253732NCI NIH HHS K00 CA253732NCI NIH HHS P30 CA013148NCI NIH HHS P30 CA044579NCI NIH HHS R01 CA060499NIH HHS R01 CA60499University of Virginia Wagner fellowship
6 · The paper itself

Abstract

The six-subunit ORC is essential for the initiation of DNA replication in eukaryotes. Cancer cell lines in culture can survive and replicate DNA replication after genetic inactivation of individual ORC subunits, ORC1, ORC2, or ORC5. In primary cells, ORC1 was dispensable in the mouse liver for endo-reduplication, but this could be explained by the ORC1 homolog, CDC6, substituting for ORC1 to restore functional ORC. Here, we have created mice with a conditional deletion of ORC2, which does not have a homolog. Although mouse embryo fibroblasts require ORC2 for proliferation, mouse hepatocytes synthesize DNA in cell culture and endo-reduplicate in vivo without ORC2. Mouse livers endo-reduplicate after simultaneous deletion of ORC1 and ORC2 both during normal development and after partial hepatectomy. Since endo-reduplication initiates DNA synthesis like normal S phase replication these results unequivocally indicate that primary cells, like cancer cell lines, can load MCM2-7 and initiate replication without ORC.

Indexed as

DNA ReplicationHepatocytesOrigin Recognition ComplexAnimalsCells, CulturedEndoreduplicationLiverMiceOrigin Recognition Complexcell biologygeneticsgenomicsmousemouse embryo fibroblastsmouse liverprimary hepatocytes

Identifiers

PMID40304571
PMCPMC12043314

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.