Role of poly(ADP-ribose) polymerase in cell-cycle checkpoint mechanisms following γ-irradiation
Biochimie, ISSN: 0300-9084, Vol: 77, Issue: 6, Page: 462-465
1995
- 59Citations
- 25Captures
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Metrics Details
- Citations59
- Citation Indexes59
- 59
- CrossRef44
- Captures25
- Readers25
- 25
Article Description
A nuclear poly(ADP-ribose) polymerase (PARP) is activated by γ-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 γ-irradiation. We found that PARP inhibitors including 3-aminobenzamide (3-AB) suppressed G1 arrest and enhanced G2 arrest following γ-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 γ-irradiation was not inhibited but the p53-responsive transient increases of WAFI/CIPI/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 WAFI/CIPI/p21 and MDM-2 mRNA expression.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/0300908496881612; http://dx.doi.org/10.1016/0300-9084(96)88161-2; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0029112163&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/7578430; https://linkinghub.elsevier.com/retrieve/pii/0300908496881612; http://dx.doi.org/10.1016/0300-9084%2896%2988161-2; https://dx.doi.org/10.1016/0300-9084%2896%2988161-2
Elsevier BV
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