ArticleeLife2021
The human origin recognition complex is essential for pre-RC assembly, mitosis, and maintenance of nuclear structure.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- A new model for coordinating the functions of TIMELESS at the replication fork.bioRxiv : the preprint server for biology · 2025Article
- Diagnostic performance of serum origin recognition complex subunit 1 protein for hepatitis B virus-related hepatocellular carcinoma.World journal of gastroenterology · 2025Article
- Unexpected molecular mechanism of Orc6-based Meier-Gorlin syndrome: insights from a humanized Drosophila model.Genetics · 2025Article
- Regulation of epigenetics and chromosome structure by human ORC2.Cell reports · 2025Article
- Specific origin selection and excess functional MCM2-7 loading in ORC-deficient cells.Nucleic acids research · 2025Article
- DivergentLife science alliance · 2025Article
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- Combination of AID2 and BromoTag expands the utility of degron-based protein knockdowns.EMBO reports · 2024Article
- Multiple pathways for licensing human replication origins.bioRxiv : the preprint server for biology · 2024Article
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- ORChestra coordinates the replication and repair music.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- The non-catalytic role of DNA polymerase epsilon in replication initiation in human cells.Nature communications · 2022Article
- The consequences of differential origin licensing dynamics in distinct chromatin environments.Nucleic acids research · 2022Article
- Orc6 is a component of the replication fork and enables efficient mismatch repair.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Replication initiation: Implications in genome integrity.DNA repair · 2021Review
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Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The origin recognition complex (ORC) cooperates with CDC6, MCM2-7, and CDT1 to form pre-RC complexes at origins of DNA replication. Here, using tiling-sgRNA CRISPR screens, we report that each subunit of ORC and CDC6 is essential in human cells. Using an auxin-inducible degradation system, we created stable cell lines capable of ablating ORC2 rapidly, revealing multiple cell division cycle phenotypes. The primary defects in the absence of ORC2 were cells encountering difficulty in initiating DNA replication or progressing through the cell division cycle due to reduced MCM2-7 loading onto chromatin in G1 phase. The nuclei of ORC2-deficient cells were also large, with decompacted heterochromatin. Some ORC2-deficient cells that completed DNA replication entered into, but never exited mitosis. ORC1 knockout cells also demonstrated extremely slow cell proliferation and abnormal cell and nuclear morphology. Thus, ORC proteins and CDC6 are indispensable for normal cellular proliferation and contribute to nuclear organization.
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Registered trials
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.