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  • 标题:The human Rad9–Rad1–Hus1 checkpoint complex stimulates flap endonuclease 1
  • 本地全文:下载
  • 作者:Wensheng Wang ; Patrick Brandt ; Marie L. Rossi
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2004
  • 卷号:101
  • 期号:48
  • 页码:16762-16767
  • DOI:10.1073/pnas.0407686101
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The toroidal damage checkpoint complex Rad9-Rad1-Hus1 (9-1-1) has been characterized as a sensor of DNA damage. Flap endonuclease 1 (FEN1) is a structure-specific nuclease involved both in removing initiator RNA from Okazaki fragments and in DNA repair pathways. FEN1 activity is stimulated by proliferating cell nuclear antigen (PCNA), a toroidal sliding clamp that acts as a platform for DNA replication and repair complexes. We show that 9-1-1 also binds and stimulates FEN1. Stimulation is observed on a variety of flap, nick, and gapped substrates simulating repair intermediates. Blocking 9-1-1 entry to the double strands prevents a portion of the stimulation. Like PCNA stimulation, 9-1-1 stimulation cannot circumvent the tracking mechanism by which FEN1 enters the substrate; however, 9-1-1 does not substitute for PCNA in the stimulation of DNA polymerase {beta}. This suggests that 9-1-1 is a damage-specific activator of FEN1.
  • 关键词:DNA damage response ; DNA replication
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