Role of poly(ADP-ribose) polymerase in cell-cycle checkpoint mechanisms following gamma-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.

journal_name

Biochimie

journal_title

Biochimie

authors

Masutani M,Nozaki T,Wakabayashi K,Sugimura T

doi

10.1016/0300-9084(96)88161-2

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

462-5

issue

6

eissn

0300-9084

issn

1638-6183

pii

0300-9084(96)88161-2

journal_volume

77

pub_type

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