ArticleNucleic acids research2018
Separase prevents genomic instability by controlling replication fork speed.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Separase activity distribution can be a marker of major molecular response and proliferation of CD34Annals of hematology · 2020Trial
- UCHL3 induces radiation resistance and acquisition of mesenchymal phenotypes by deubiquitinating POLD4 in glioma stem cells.Cellular and molecular life sciences : CMLS · 2024Article
- Synthetic Lethality between Cohesin and WNT Signaling Pathways in Diverse Cancer Contexts.Cells · 2024Article
- Gene Expression Pattern ofCancers · 2023Article
- Disease-associated c-MYC downregulation in human disorders of transcriptional regulation.Human molecular genetics · 2022Article
- The multifaceted roles of cohesin in cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- The Interplay of Cohesin and the Replisome at Processive and Stressed DNA Replication Forks.Cells · 2021Review
- Functional Coupling between DNA Replication and Sister Chromatid Cohesion Establishment.International journal of molecular sciences · 2021Review
- Cornelia de Lange syndrome: from molecular diagnosis to therapeutic approach.Journal of medical genetics · 2020Review
- Chromosome Missegregation in Single Human Oocytes Is Related to the Age and Gene Expression Profile.International journal of molecular sciences · 2020Article
- The function of histone acetylation in cervical cancer development.Bioscience reports · 2019Review
- Overexpression of the cohesin-core subunit SMC1A contributes to colorectal cancer development.Journal of experimental & clinical cancer research : CR · 2019Article
- Genome-wide analysis of the spatiotemporal regulation of firing and dormant replication origins in human cells.Nucleic acids research · 2018Article
- Article
- Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function.PLoS genetics · 2018Article
- Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis.
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