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首页> 外文期刊>Nucleus >Binding kinetics of human ISWI chromatin-remodelers to DNA repair sites elucidate their target location mechanism
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Binding kinetics of human ISWI chromatin-remodelers to DNA repair sites elucidate their target location mechanism

机译：人类ISWI染色质重塑剂与DNA修复位点的结合动力学阐明了其靶标定位机制

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Chromatin remodelers translocate nucleosomes along the DNA chain in an ATP-dependent manner. This catalytic activity is particularly important for DNA replication and repair since both processes require a significant amount of nucleosome translocations and assembly during DNA synthesis. Recently, we have studied the mobility and interactions of the human ISWI family chromatin remodelers Snf2H and Snf2L as well as Acf1, one of the non-catalytic subunits present in the ACF and CHRAC complexes of Snf2H. We proposed that these protein complexes identify their nucleosomal substrates via a continuous sampling mechanism. It rationalizes the relatively high nuclear mobility and abundance observed for all ISWI proteins in terms of fast target location. According to our model a certain type of ISWI complex visits a given nucleosome in the human genome on the timescale of several seconds to a few minutes. Here, we show that the ISWI proteins Snf2H, Snf2L as well as Acf1 accumulate at UV-induced DNA damage sites within seconds and reach a plateau after a few minutes. These findings corroborate the predictions of the continuous sampling mechanism as an efficient way for targeting chromatin remodelers to sites in the genome that require their activity. In comparison to the mobility of PCNA (proliferating cell nuclear antigen) that also accumulates at DNA repair sites the specifics of substrate location by chromatin remodelers are further characterized.
机译：染色质重塑剂以ATP依赖性方式沿DNA链转移核小体。这种催化活性对于DNA复制和修复特别重要，因为这两个过程都需要在DNA合成过程中进行大量的核小体移位和组装。最近，我们研究了人类ISWI家族染色质重塑剂Snf2H和Snf2L以及Acf1（存在于Snf2H的ACF和CHRAC复合物中的非催化亚基之一）的迁移率和相互作用。我们提出这些蛋白质复合物通过连续采样机制确定其核小体底物。就快速靶标定位而言，它合理化了所有ISWI蛋白相对较高的核迁移率和丰度。根据我们的模型，某种类型的ISWI复合物会在几秒钟到几分钟的时间内访问人类基因组中的给定核小体。在这里，我们显示ISWI蛋白Snf2H，Snf2L以及Acf1会在几秒钟内积聚在UV诱导的DNA损伤部位，并在几分钟后达到稳定水平。这些发现证实了连续采样机制的预测是将染色质重塑剂靶向基因组中需要其活性的位点的有效途径。与也积累在DNA修复位点的PCNA（增殖细胞核抗原）的迁移率相比，通过染色质重塑剂对底物位置的特异性进行了进一步表征。

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