ArticleNucleic acids research2016
New origin firing is inhibited by APC/CCdh1 activation in S-phase after severe replication stress.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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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.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Improved detection of DNA replication fork-associated proteins.Cell reports · 2024Article
- The Interfascicular Matrix of Energy Storing Tendons Houses Heterogenous Cell Populations Disproportionately Affected by Aging.Aging and disease · 2024Article
- Article
- RAD51 is a druggable target that sustains replication fork progression upon DNA replication stress.PloS one · 2022Article
- Replication stress response defects are associated with response to immune checkpoint blockade in nonhypermutated cancers.Science translational medicine · 2021Article
- Control of replication stress and mitosis in colorectal cancer stem cells through the interplay of PARP1, MRE11 and RAD51.Cell death and differentiation · 2021Article
- Nucleotide depletion reveals the impaired ribosome biogenesis checkpoint as a barrier against DNA damage.The EMBO journal · 2020Article
- Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse.Cellular and molecular life sciences : CMLS · 2020Article
- Activating the Anaphase Promoting Complex to Enhance Genomic Stability and Prolong Lifespan.International journal of molecular sciences · 2018Review
- Integrated analysis highlights APC11 protein expression as a likely new independent predictive marker for colorectal cancer.Scientific reports · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defects in DNA replication and repair are known to promote genomic instability, a hallmark of cancer cells. Thus, eukaryotic cells have developed complex mechanisms to ensure accurate duplication of their genomes. While DNA damage response has been extensively studied in tumour cells, the pathways implicated in the response to replication stress are less well understood especially in non-transformed cells. Here we show that in non-transformed cells, APC/C(Cdh1) is activated upon severe replication stress. Activation of APC/C(Cdh1) prevents new origin firing and induces permanent arrest in S-phase. Moreover, Rad51-mediated homologous recombination is also impaired under these conditions. APC/C(Cdh1) activation in S-phase occurs after replication forks have been processed into double strand breaks. Remarkably, this activation, which correlates with decreased Emi1 levels, is not prevented by ATR/ATM inhibition, but it is abrogated in cells depleted of p53 or p21. Importantly, we found that the lack of APC/C(Cdh1) activity correlated with an increase in genomic instability. Taken together, our results define a new APC/C(Cdh1) function that prevents cell cycle resumption after prolonged replication stress by inhibiting origin firing, which may act as an additional mechanism in safeguarding genome integrity.
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