ArticleMolecular cell2014
Suppression of genome instability in pRB-deficient cells by enhancement of chromosome cohesion.
Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- RB loss modulates chromatin organization by regulating cohesin-dependent loops and enhancer-promoter interactions.Nature communications · 2026Article
- RB dependent transcriptional regulation at mitotic centromeres preserves genome stability.Life science alliance · 2026Article
- Review
- Therapeutic Strategies for RB1-Deficient Cancers: Intersecting Gene Regulation and Targeted Therapy.Cancers · 2024Review
- Patterns in the tapestry of chromatin-bound RB.Trends in cell biology · 2024Review
- Determinants of Aurora kinase B inhibitor sensitivity in small cell lung cancer.Translational lung cancer research · 2024Article
- RB loss sensitizes cells to replication-associated DNA damage after PARP inhibition by trapping.Life science alliance · 2023Article
- Seeing is believing: the impact of RB on nuclear organization.Cell cycle (Georgetown, Tex.) · 2023Article
- Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers.Molecular cancer research : MCR · 2023Article
- Suppression of chromosome instability by targeting a DNA helicase in budding yeast.Molecular biology of the cell · 2023Article
- Chromatin-bound RB targets promoters, enhancers, and CTCF-bound loci and is redistributed by cell-cycle progression.Molecular cell · 2022Article
- Reduced sister chromatid cohesion acts as a tumor penetrance modifier.PLoS genetics · 2022Article
- Genome maintenance in retinoblastoma: Implications for therapeutic vulnerabilities.Oncology letters · 2022Review
- Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Retinoblastoma protein regulates carcinogen susceptibility at heterochromatic cancer driver loci.Life science alliance · 2022Article
- Active RB causes visible changes in nuclear organization.The Journal of cell biology · 2022Article
- Clinically relevant fusion oncogenes: detection and practical implications.Therapeutic advances in medical oncology · 2022Review
- The Interplay of Cohesin and the Replisome at Processive and Stressed DNA Replication Forks.Cells · 2021Review
- Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma.Nature communications · 2021Article
- Suv420 enrichment at the centromere limits Aurora B localization and function.Journal of cell science · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Chromosome instability (CIN), a common feature of solid tumors, promotes tumor evolution and increases drug resistance during therapy. We previously demonstrated that loss of the retinoblastoma protein (pRB) tumor suppressor causes changes in centromere structure and generates CIN. However, the mechanism and significance of this change was unclear. Here, we show that defects in cohesion are key to the pRB loss phenotype. pRB loss alters H4K20 methylation, a prerequisite for efficient establishment of cohesion at centromeres. Changes in cohesin regulation are evident during S phase, where they compromise replication and increase DNA damage. Ultimately, such changes compromise mitotic fidelity following pRB loss. Remarkably, increasing cohesion suppressed all of these phenotypes and dramatically reduced CIN in cancer cells lacking functional pRB. These data explain how loss of pRB undermines genomic integrity. Given the frequent functional inactivation of pRB in cancer, conditions that increase cohesion may provide a general strategy to suppress CIN.
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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.