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Role of poly(ADP-ribose) polymerase in cell-cycle checkpoint mechanisms following γ-irradiation
Abstract
A nuclear poly(ADP-ribose) polymerase (PARP) is activated by gamma-irradiation and consequently synthesizes poly(ADP-ribose) by binding to DNA strand-breaks. This property suggests that PARP is a DNA strand-break-signal generator. Meanwhile, the cell-cycle arrest occurs in G1 and G2 phases following gamma-irradiation. We found that PARP inhibitors including 3-aminobenzamide (3-AB) suppressed G1 arrest and enhanced G2 arrest following gamma-irradiation. These observations suggested that PARP is critical for the induction of G1 arrest and is also involved in the regulation of G2 arrest. Furthermore, the effects of 3-AB on the G1-arrest signal-transduction pathway were also studied. We found that p53 stabilization following gamma-irradiation was not inhibited but the p53-responsive transient increases of WAF1/CIP1/p21 and MDM-2 mRNA were suppressed by 3-AB. Therefore, it is suggested that PARP participates in G1-arrest signal-transduction pathway through the modulation of WAF1/CIP1/p21 and MDM-2 mRNA expression.
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“These processes are well-known to happen in response to PARP inhibition and depict the biggest part of the network (Ray Chaudhuri and Nussenzweig, 2017; Masutani et al, 1995).”
From Network integration of thermal proteome profiling with multi-omics data decodes PARP inhibition (2024) · cites this paper as Masutani et al, 1995
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Metadata
- Authors
- Masutani, M., Nozaki, T., Wakabayashi, K., & Sugimura, T.
- Affiliations
- National Cancer Center Research Institute (JP)
- Venue
- Biochimie
- Publisher
- Elsevier BV
- Published
- 1995
- Volume
- 77
- Issue
- 6
- Pages
- 462-465
- ISSN
- 0037-9042 (ISSN-L)
- 0300-9084
- OpenAlex
- W1965795362
- Cited by
- 61
- References
- 27
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimie (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, Labour and Welfare
- Foundation for Promotion of Cancer Research
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- poly(ADP-ribose) polymerase, gamma irradiation, cell cycle checkpoints, G1 cell cycle arrest, G2 cell cycle arrest, 3-aminobenzamide, PARP inhibitors, DNA strand breaks, p53 stabilization, MDM2, signal transduction, DNA damage response
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Animals, DNA Damage, Enzyme Activation, Gamma Rays, Humans, Poly(ADP-ribose) Polymerases, Radiation-Sensitizing Agents, Signal Transduction, G1 Phase, G2 Phase
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