PDF(Pubmed)
Abstract：
RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation. Interestingly, in response to DNA double-stranded breaks (DSBs), α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner, and these DSB-induced α-satellite RNAs form into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.
摘要：
RNA聚合酶（RNAP）II在非编码重复卫星DNA上的转录在染色体分离中起重要作用，但是对卫星转录的调控知之甚少。我们在这里显示拓扑异构酶I(TopI)，不是TopII,促进α-卫星DNA的转录，人类着丝粒上卫星DNA的主要类型。机械上,TopI定位于着丝粒，结合RNAPII并促进RNAPII延伸。有趣的是,响应DNA双链断裂（DSB），α-卫星转录以不依赖DNA损伤检查点但依赖TopI的方式受到极大刺激，这些DSB诱导的α卫星RNA在细胞核中形成强烈的斑点。值得注意的是,TopI依赖性卫星转录也存在于小鼠3T3和果蝇S2细胞以及果蝇幼虫想象翼盘和肿瘤组织中。总之,我们的发现揭示了一种进化保守的机制，其中TopI是细胞和动物水平上调节卫星转录的关键参与者。
