BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression.

BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression.
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DOI:
10.1093/nar/gkq559
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发表时间:
2010-11
影响因子:
14.9
通讯作者:
Bultman SJ
Bultman SJ
中科院分区:
生物学2区
文献类型:
--
作者:
Cohen SM;Chastain PD 2nd;Rosson GB;Groh BS;Weissman BE;Kaufman DG;Bultman SJ

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为了使DNA复制发生,染色质必须被重塑。然而,我们对哪些蛋白质改变核小体在起点和复制叉的占有率以及它们在复制的哪些方面是必需的知之甚少。在这里,我们证明了BRG 1的哺乳动物SWI/SNF相关复合物的催化亚基共定位与起源识别复合物,GINS复合物,和增殖细胞核抗原在DNA复制的扩展染色质纤维的网站。BRG 1占据的特定模式表明它不参与起点选择,但参与起点的发射和复制延伸的过程。Brg 1突变小鼠胚胎和RNAi敲低细胞表现出复制叉进展率降低50%的事实证实了后一种功能,这与细胞增殖降低有关。BRG 1的这种新功能与其在胚胎发生过程中的需求及其作为肿瘤抑制因子维持基因组稳定性和预防癌症的作用一致。
For DNA replication to occur, chromatin must be remodeled. Yet, we know very little about which proteins alter nucleosome occupancy at origins and replication forks and for what aspects of replication they are required. Here, we demonstrate that the BRG1 catalytic subunit of mammalian SWI/SNF-related complexes co-localizes with origin recognition complexes, GINS complexes, and proliferating cell nuclear antigen at sites of DNA replication on extended chromatin fibers. The specific pattern of BRG1 occupancy suggests it does not participate in origin selection but is involved in the firing of origins and the process of replication elongation. This latter function is confirmed by the fact that Brg1 mutant mouse embryos and RNAi knockdown cells exhibit a 50% reduction in replication fork progression rates, which is associated with decreased cell proliferation. This novel function of BRG1 is consistent with its requirement during embryogenesis and its role as a tumor suppressor to maintain genome stability and prevent cancer.
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