ArticleNucleic acids research2016
Reduced cohesin destabilizes high-level gene amplification by disrupting pre-replication complex bindings in human cancers with chromosomal instability.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Activation of KIT signaling promotes early tumorigenesis through the AP-1 pathway in APC/TP53 double-knockout human colon organoids.Cell death & disease · 2026Article
- SMARCA4 activation engages FOSL1 to drive enhancer reprogramming and tumorigenic phenotypes in SMARCA4-deficient LUAD cells.Cell death discovery · 2026Article
- Epigenetic Regulation of Higher-Order Chromatin Structure (HOCS) and Its Implication in Human Diseases.Cancers · 2026Review
- Aberrant cohesin function in Saccharomyces cerevisiae activates Mcd1 degradation to promote cell lethality.PLoS genetics · 2025Article
- Aberrant cohesin function inbioRxiv : the preprint server for biology · 2025Article
- Identifying TP53RK as a key regulator of colorectal cancer survival and a potential therapeutic target.Scientific reports · 2025Article
- ACTL6A depletion induces KLF4-mediated anti-tumorigenic effects in colorectal cancer.Cell death & disease · 2025Article
- Intergenic sequences harboring potential enhancer elements contribute to Axenfeld-Rieger syndrome by regulating PITX2.JCI insight · 2024Article
- Role of chromosomal cohesion and separation in aneuploidy and tumorigenesis.Cellular and molecular life sciences : CMLS · 2024Review
- EMT-mediated regulation of CXCL1/5 for resistance to anti-EGFR therapy in colorectal cancer.Oncogene · 2022Article
- The Interplay of Cohesin and RNA Processing Factors: The Impact of Their Alterations on Genome Stability.International journal of molecular sciences · 2022Review
- The multifaceted roles of cohesin in cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- A Deep Neural Network for Gastric Cancer Prognosis Prediction Based on Biological Information Pathways.Journal of oncology · 2022Article
- Cohesin Mutations in Cancer: Emerging Therapeutic Targets.International journal of molecular sciences · 2021Review
- Article
- Review
- Aberrant GATA2 epigenetic dysregulation induces a GATA2/GATA6 switch in human gastric cancer.Oncogene · 2018Article
- CTCF, Cohesin, and Chromatin in Human Cancer.Genomics & informatics · 2017Review
- Characterization of a Novel MMS-Sensitive Allele of Schizosaccharomyces pombe mcm4.G3 (Bethesda, Md.) · 2016Article
- Dynamic cohesin-mediated chromatin architecture controls epithelial-mesenchymal plasticity in cancer.EMBO reports · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene amplification is a hallmark of cancer with chromosomal instability although the underlying mechanism by which altered copy numbers are maintained is largely unclear. Cohesin, involved in sister chromatid cohesion, DNA repair, cell cycle progression and transcriptional regulation of key developmental genes, is frequently overexpressed in human cancer. Here we show that cohesin-dependent change in DNA replication controls the copy numbers of amplified genes in cancer cells with chromosomal instability. We found that the down-regulation of elevated cohesin leads to copy number-associated gene expression changes without disturbing chromosomal segregation. Highly amplified genes form typical long-range chromatin interactions, which are stabilized by enriched cohesin. The spatial proximities among cohesin binding sites within amplified genes are decreased by RAD21-knockdown, resulting in the rapid decline of amplified gene expression. After several passages, cohesin depletion inhibits DNA replication initiation by reducing the recruitment of pre-replication complexes such as minichromosome maintenance subunits 7 (MCM7), DNA polymerase α, and CDC45 at replication origins near the amplified regions, and as a result, decreases the DNA copy numbers of highly amplified genes. Collectively, our data demonstrate that cohesin-mediated chromatin organization and DNA replication are important for stabilizing gene amplification in cancer cells with chromosomal instability.
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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.