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

NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells
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DOI:
10.1016/j.bbrc.2010.05.063
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发表时间:
2010-06-25
影响因子:
3.1
通讯作者:
Ozaki, Toshinori
Ozaki, Toshinori
中科院分区:
生物学4区
文献类型:
--
作者:
Bu, Youquan;Suenaga, Yusuke;Ozaki, Toshinori

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NFBD 1/MDC 1是一种大型核蛋白,参与对DNA损伤的早期细胞反应。当DNA损伤时,NFBD 1具有促进有效DNA修复的能力。在本研究中,我们发现,除了DNA损伤反应,NFBD 1在G2/M转换的调节中起着关键作用。使用同步化HeLa细胞的表达研究表明,与有丝分裂激酶Plk 1一样,NFBD 1的表达水平在细胞周期的G2/M期最高。siRNA介导的NFBD 1敲低导致G2/M期阻滞以及与γ H2 AX和促凋亡p73的量显著增加相关的同时凋亡。由于在NFBD 1敲低的细胞中可检测到有丝分裂磷酸化组蛋白H3的显著下调,因此NFBD 1的敲低可能抑制G2/M转换。综上所述,我们目前的研究结果表明,NFBD 1在调节适当的有丝分裂进入中具有关键作用。(C)2010年爱思唯尔公司All rights reserved.
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.