ArticleThe Journal of biological chemistry2020
A human cancer cell line initiates DNA replication normally in the absence of ORC5 and ORC2 proteins.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Origin recognition complex subunit 1 functions as an oncogenic driver and therapeutic target in cancer.Discover oncology · 2025Review
- A novel disulfidptosis-related mRNA signature predicts prognosis and therapeutic response in lung squamous cell carcinoma.BMC pulmonary medicine · 2025Article
- A Trade-Off between Body Mass and Cancer Resistance in Cetaceans Is Mediated by Cell Cycle-Related Gene Evolution.Molecular biology and evolution · 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
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- Multiple pathways for licensing human replication origins.bioRxiv : the preprint server for biology · 2024Article
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- Developmentally Programmed Switches in DNA Replication: Gene Amplification and Genome-Wide Endoreplication inMicroorganisms · 2023Article
- Systemic analysis of the DNA replication regulator origin recognition complex in lung adenocarcinomas identifies prognostic and expression significance.Cancer medicine · 2023Article
- Multi-omic insights into the cellular response ofFrontiers in plant science · 2023Article
- CRISPR/Cas9 Genome-Editing Technology and Potential Clinical Application in Gastric Cancer.Genes · 2022Review
- Bioinformatics Analysis of RNA-seq Data Reveals Genes Related to Cancer Stem Cells in Colorectal Cancerogenesis.International journal of molecular sciences · 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
- Reduced RBPMS Levels Promote Cell Proliferation and Decrease Cisplatin Sensitivity in Ovarian Cancer Cells.International journal of molecular sciences · 2022Article
- NADNAR cancer · 2021Article
- Replication initiation: Implications in genome integrity.DNA repair · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The origin recognition complex (ORC), composed of six subunits, ORC1-6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2-7, the minichromosome maintenance protein complex, around DNA and initiate DNA replication. We previously reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a reduction in the number of origins firing. Here, using CRISPR-Cas9-mediated mutations, we report that human HCT116 colon cancer cells also survive when ORC5 protein expression is abolished via a mutation in the initiator ATG of the ORC5 gene. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2-7 and initiate replication from a similar number of origins as WT cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells, rendering both ORC5 and ORC2 proteins undetectable in the same cells and destabilizing the ORC1, ORC3, and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2-7 normally to chromatin, and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2-7 to initiate DNA replication, or human cell lines can sometimes recruit MCM2-7 to origins independent of ORC.
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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.