Chromatin stiffening underlies enhanced locus mobility after DNA damage in budding yeast
Chromatin stiffening underlies enhanced locus mobility after DNA damage in budding yeast
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DOI：
10.15252/embj.201695842
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发表时间：
2017-09-01
期刊：
影响因子：
11.4
通讯作者：
Zimmer, Christophe
中科院分区：
文献类型：
--
作者：
Herbert, Sebastien;Brion, Alice;Zimmer, Christophe
DNA 双链断裂 (DSB) 会诱导细胞反应，涉及受损位点的组蛋白修饰和染色质重塑，并增加受损位点局部和细胞核内整体的染色体动力学。与此同时，我们已经清楚，染色体的空间组织和动力学在很大程度上可以通过束缚但随机移动的聚合物链的统计特性来解释，其主要特征是其刚性和压缩性。然而，DNA 损伤期间染色质的这些特性如何受到影响仍不清楚。在这里，我们使用活细胞显微镜来追踪染色质位点，并测量数千个细胞中酵母 IV 号染色体上位点之间的距离，无论是否存在基因毒性应激。我们证实 DSB 会导致染色质亚扩散增强，并表明染色体内距离随着整个染色体上的 DNA 损伤而增加。我们的数据可以通过染色质刚性的增加来解释，但不能仅通过染色质解缩或着丝粒解链来解释。我们提供的证据表明染色质硬化部分是由组蛋白 H2A 磷酸化介导的。我们的结果支持染色质纤维在全基因组范围内变硬，这是 DNA 损伤的结果，也是染色质迁移率增加的一种新机制。
DNA double-strand breaks (DSBs) induce a cellular response that involves histone modifications and chromatin remodeling at the damaged site and increases chromosome dynamics both locally at the damaged site and globally in the nucleus. In parallel, it has become clear that the spatial organization and dynamics of chromosomes can be largely explained by the statistical properties of tethered, but randomly moving, polymer chains, characterized mainly by their rigidity and compaction. How these properties of chromatin are affected during DNA damage remains, however, unclear. Here, we use live cell microscopy to track chromatin loci and measure distances between loci on yeast chromosome IV in thousands of cells, in the presence or absence of genotoxic stress. We confirm that DSBs result in enhanced chromatin subdiffusion and show that intrachromosomal distances increase with DNA damage all along the chromosome. Our data can be explained by an increase in chromatin rigidity, but not by chromatin decondensation or centromeric untethering only. We provide evidence that chromatin stiffening is mediated in part by histone H2A phosphorylation. Our results support a genome-wide stiffening of the chromatin fiber as a consequence of DNA damage and as a novel mechanism underlying increased chromatin mobility.