ArticleOncogene2010
Reducing MCM levels in human primary T cells during the G(0)-->G(1) transition causes genomic instability during the first cell cycle.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Trial
- Allelic bias contributes to heterogeneous phenotypes of NK cell deficiency.Cell reports · 2025Article
- Loss of G1-phase CDK-inhibition biases instability between genomic regions by unevenly reducing activity among replication origins.iScience · 2025Article
- Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.Cancer metastasis reviews · 2024Review
- APC/C prevents a noncanonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Chalkiness and premature controlled by energy homeostasis in OsNAC02 Ko-mutant during vegetative endosperm development.BMC plant biology · 2024Article
- APC/C prevents non-canonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.bioRxiv : the preprint server for biology · 2023Article
- Canine diffuse large b-cell lymphoma downregulates the activity of CD8 + T-cells through tumor-derived extracellular vesicles.Cancer cell international · 2023Article
- Article
- Mcm2 hypomorph leads to acute leukemia or hematopoietic stem cell failure, dependent on genetic context.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Quantitative profiling of adaptation to cyclin E overproduction.Life science alliance · 2022Article
- Targeting KRAS4A splicing through the RBM39/DCAF15 pathway inhibits cancer stem cells.Nature communications · 2021Article
- CDC45 modulates MCM7 expression and inhibits cell proliferation by suppressing the PI3K/AKT pathway in acute myeloid leukemia.American journal of translational research · 2021Article
- Review
- Cellular Mechanisms and Regulation of Quiescence.Developmental cell · 2020Review
- Article
- A unique mutator phenotype reveals complementary oncogenic lesions leading to acute leukemia.JCI insight · 2019Article
- Intrinsic checkpoint deficiency during cell cycle re-entry from quiescence.The Journal of cell biology · 2019Article
- Investigating the role of Rts1 in DNA replication initiation.Wellcome open research · 2018Article
- Ets transcription factor GABP controls T cell homeostasis and immunity.Nature communications · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
DNA replication is tightly regulated, but paradoxically there is reported to be an excess of MCM DNA replication proteins over the number of replication origins. Here, we show that MCM levels in primary human T cells are induced during the G(0)-->G(1) transition and are not in excess in proliferating cells. The level of induction is critical as we show that a 50% reduction leads to increased centromere separation, premature chromatid separation (PCS) and gross chromosomal abnormalities typical of genomic instability syndromes. We investigated the mechanisms involved and show that a reduction in MCM levels causes dose-dependent DNA damage involving activation of ATR & ATM and Chk1 & Chk2. There is increased DNA mis-repair by non-homologous end joining (NHEJ) and both NHEJ and homologous recombination are necessary for Mcm7-depleted cells to progress to metaphase. Therefore, a simple reduction in MCM loading onto DNA, which occurs in cancers as a result of aberrant cell cycle control, is sufficient to cause PCS and gross genomic instability within one cell cycle.
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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.