pRB plays an essential role in cell cycle arrest induced by DNA damage
Open accessAbstract
To maintain genome stability, cells with damaged DNA must arrest to allow repair of mutations before replication. Although several key components required to elicit this arrest have been discovered, much of the pathway remains elusive. Here we report that pRB acts as a central mediator of the proliferative block induced by a diverse range of DNA damaging stimuli. Rb −/− mouse embryo fibroblasts are defective in arrest after γ-irradiation, UV irradiation, and treatment with a variety of chemotherapeutic drugs. In contrast, the pRB related proteins p107 and p130 do not play an essential part in the DNA damage response. pRB is required specifically for the G 1 /S phase checkpoint induced by γ-irradiation. Despite a defect in G 1 /S phase arrest, levels of p53 and p21 are increased normally in Rb −/− cells in response to γ-irradiation. These results lead us to propose a model in which pRB acts as an essential downstream target of the DNA damage-induced arrest pathway. The ability of pRB to prevent replication of damaged DNA is likely to inhibit the propagation of carcinogenic mutations and may therefore contribute to its role as a tumor suppressor. Furthermore, because many cancer therapies act by damaging DNA, these findings also have implications for the treatment of tumors in which pRB is inactivated.
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RB is required for cell cycle arrest.
“As for p21, RB is also required for cell cycle arrest.100, 152”
From Census and evaluation of p53 target genes (2017) · cites this paper as [152]
Rb-deficient cells fail to properly arrest in G1 upon DNA damage and may replicate mutated DNA, leading to accumulation of mutations.
“Rb-deficient cells fail to properly arrest in G1 upon DNA damage and might replicate mutated DNA, leading to the accumulation of mutations102,105,111,116.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [116]
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- Authors
- Harrington, E. A., Bruce, J. L., Harlow, E., & Dyson, N.
- Affiliations
- Massachusetts General Hospital (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-09-29
- Volume
- 95
- Issue
- 20
- Pages
- 11945-11950
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC21745
- OpenAlex
- W2150451425
- Cited by
- 242
- References
- 53
- Citations by year
- 2026: 4 · 2025: 1 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 10 · 2013: 3 · 2012: 10
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- retinoblastoma protein, DNA damage response, cell cycle arrest, G1/S checkpoint, gamma irradiation, UV irradiation, chemotherapeutic drugs, p107, p130, p53, p21, genome stability, tumor suppressor
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Cell Cycle, Cells, Cultured, DNA Damage, DNA Repair, Gamma Rays, Mitosis, Models, Biological, Nuclear Proteins, Phosphoproteins, Proteins, Vinblastine, Vincristine, Gene Expression, Retinoblastoma Protein, Genes, Retinoblastoma, Mice, Knockout, Retinoblastoma-Like Protein p130, Retinoblastoma-Like Protein p107, Mice
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