The role of the Mus81-Eme1 endonuclease in homologous recombination

DOI

Bibliographic Information

Other Title
  • 相同組換えにおけるMus81-Eme1 endonucleaseの役割

Abstract

The Mus81-Eme1 complex is a structure specific endonuclease that belongs to the XPF-ERCC1 superfamily, preferentially cleaving aberrant fork structures. Because ERCC1 is now considered to be a potential target of cisplatin-based chemotherapy and radiochemotherapy, it is of great importance to understand the role of the complex in cancer. In order to investigate the role of the complex in human cancer cells, the genes were knocked out in the colon cancer cell line HCT116. Deficiency of both genes led to decreases in sister chromatid exchanges and gene targeting frequency, indicating a role of the complex in homologous recombination. Hypersensitivity to mitomycin C and cisplatin but not to other DNA damaging agents was observed in the knockout cells, suggesting that Mus81-Eme1 is specifically involved in the rescue of stalled replication fork generated by DNA cross-linking. Consistent with its role during DNA replication, the intra-S phase checkpoint pathways mediated by Chk1 and Chk2 were activated in the mutant cells. These findings support the biochemical evidence that Mus81-Eme1 plays a critical role in processing stalled replication forks by the endonuclease activity.

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Details 詳細情報について

  • CRID
    1390001205641426816
  • NII Article ID
    130007000895
  • DOI
    10.11513/jrrsabst.2007.0.56.0
  • Text Lang
    ja
  • Data Source
    • JaLC
    • CiNii Articles
  • Abstract License Flag
    Disallowed

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