2008年12月
PARP-1 ensures regulation of replication fork progression by homologous recombination on damaged DNA
JOURNAL OF CELL BIOLOGY
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- 巻
- 183
- 号
- 7
- 開始ページ
- 1203
- 終了ページ
- 1212
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1083/jcb.200806068
- 出版者・発行元
- ROCKEFELLER UNIV PRESS
Poly-ADP ribose polymerase 1 (PARP-1) is activated by DNA damage and has been implicated in the repair of single-strand breaks (SSBs). Involvement of PARP-1 in other DNA damage responses remains controversial. In this study, we show that PARP-1 is required for replication fork slowing on damaged DNA. Fork progression in PARP-1(-/-) DT40 cells is not slowed down even in the presence of DNA damage induced by the topoisomerase I inhibitor camptothecin (CPT). Mammalian cells treated with a PARP inhibitor or PARP-1-specific small interfering RNAs show similar results. The expression of human PARP-1 restores fork slowing in PARP-1(-/-) DT40 cells. PARP-1 affects SSB repair, homologous recombination (HR), and nonhomologous end joining; there fore, we analyzed the effect of CPT on DT40 clones deficient in these pathways. We. find that fork slowing is correlated with the proficiency of HR-mediated repair. Our data support the presence of a novel checkpoint pathway in which the initiation of HR but not DNA damage delays the fork progression.
- リンク情報
- ID情報
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- DOI : 10.1083/jcb.200806068
- ISSN : 0021-9525
- Web of Science ID : WOS:000262269700005