4.6 Article

NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells

期刊

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.05.063

关键词

Apoptosis; Cell cycle arrest; siRNA; NFBD1; p73

资金

  1. Ministry of Health, Labour and Welfare for the Third Term Comprehensive Control Research for Cancer
  2. Ministry of Education, Culture, Sports, Science and Technology, Japan
  3. Japan Society for the Promotion of Science

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NFBD1/MDC1 is a large nuclear protein involved in the early cellular response to DNA damage. Upon DNA damage, NFBD1 has an ability to facilitate the efficient DNA repair. In the present study, we have found that, in addition to DNA damage response, NFBD1 plays a critical role in the regulation of G2/M transition. Expression study using synchronized HeLa cells demonstrated that, like the mitotic kinase Plk1, NFBD1 expression level is maximal in G2/M-phase of the cell cycle. siRNA-mediated knockdown of NFBD1 resulted in G2/M arrest as well as simultaneous apoptosis in association with a significant increase in the amounts of gamma H2AX and pro-apoptotic p73. Since a remarkable down-regulation of mitotic phospho-histone H3 was detectable in NFBD1-knocked down cells, it is likely that knocking down of NFBD1 inhibits G2/M transition. Taken together, our present findings suggest that NFBD1 has a pivotal role in the regulation of proper mitotic entry. (C) 2010 Elsevier Inc. All rights reserved.

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