Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest.
Open accessAbstract
The tumor suppressor p53 contributes to maintaining genome stability by inducing a cell cycle arrest or apoptosis in response to conditions that generate DNA damage. Nuclear injection of linearized plasmid DNA, circular DNA with a large gap, or single-stranded circular phagemid is sufficient to induce a p53-dependent arrest. Supercoiled and nicked plasmid DNA, and circular DNA with a small gap were ineffective. Titration experiments indicate that the arrest mechanism in normal human fibroblasts can be activated by very few double strand breaks, and only one may be sufficient. Polymerase chain reaction assays showed that end-joining activity is low in serum-arrested human fibroblasts, and that higher joining activity occurs as cells proceed through G1 or into S phase. We propose that the exquisite sensitivity of the p53-dependent G1 arrest is partly due to inefficient repair of certain types of DNA damage in early G1.
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- Authors
- Huang, L. C., Clarkin, K. C., & Wahl, G. M.
- Affiliations
- Salk Institute for Biological Studies (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-05-14
- Volume
- 93
- Issue
- 10
- Pages
- 4827-4832
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC39364
- OpenAlex
- W2049448938
- Cited by
- 384
- References
- 57
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 12 · 2019: 8 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 11 · 2014: 16 · 2013: 14 · 2012: 11
- FWCI
- 10.45
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- p53, DNA damage sensor, G1 cell cycle arrest, DNA double-strand breaks, DNA end joining, DNA repair, genome stability, tumor suppressor, human fibroblasts, single-stranded DNA, plasmid DNA
- MeSH terms
- Base Sequence, Cell Cycle, Cell Line, DNA, DNA Damage, DNA Repair, Humans, Microinjections, Molecular Sequence Data, Plasmids, Sensitivity and Specificity, Polymerase Chain Reaction, Genes, p53, G1 Phase, DNA Primers
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