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NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells
Authors:Youquan Bu  Yusuke Suenaga  Meixiang Sang  Fangzhou Song  Toshinori Ozaki
Institution:a Division of Biochemistry and Anti-tumor Research, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan
b Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, People’s Republic of China
c Division of Biochemistry and Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan
Abstract: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 γH2AX 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.
Keywords:Apoptosis  Cell cycle arrest  siRNA  NFBD1  p73
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