Yeast high mobility group protein HMO1 stabilizes chromatin and is evicted during repair of DNA double strand breaks.
Yeast high mobility group protein HMO1 stabilizes chromatin and is evicted during repair of DNA double strand breaks.
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DOI：
10.1093/nar/gkv498
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发表时间：
2015-07-13
影响因子：
14.9
通讯作者：
Grove A
中科院分区：
文献类型：
--
作者：
Panday A;Xiao L;Grove A
DNA通过与组蛋白和结构蛋白如高迁移率族蛋白(HMGB)结合，被包装成浓缩的染色质纤维。然而，这种DNA包装减少了作用于DNA的酶的可及性，例如在双链断裂(DSB)后处理DNA的蛋白质。染色质重塑克服了这一障碍。我们在这里表明，酿酒酵母HMGB蛋白HMO1稳定染色质，这表明在没有HMGB蛋白的情况下，染色质重塑更快。在DSB修复过程中，HMO1与核心组蛋白一起被驱逐，并且在没有HMO1的情况下，染色质重构事件，如组蛋白H2A磷酸化和H3驱逐更快。促进染色质重塑反过来又与更有效的DNA切除和修复蛋白的招募相关；例如，在没有HMO1的情况下，DNA末端结合蛋白Ku的向内移位更快。这种染色质的稳定需要HMO1富含赖氨酸的C末端延伸，作为HMO1 C末端尾部表型hmo1缺失的截断。由于这使人想起哺乳动物组蛋白H1的基本C-末端结构域在染色质压缩中的需要，我们推测HMO1通过其富含赖氨酸的结构域对DNA进行弯曲和压缩来促进染色质的稳定性，并且它必须与核心组蛋白一起被驱逐，才能有效地修复DSB。
DNA is packaged into condensed chromatin fibers by association with histones and architectural proteins such as high mobility group (HMGB) proteins. However, this DNA packaging reduces accessibility of enzymes that act on DNA, such as proteins that process DNA after double strand breaks (DSBs). Chromatin remodeling overcomes this barrier. We show here that the Saccharomyces cerevisiae HMGB protein HMO1 stabilizes chromatin as evidenced by faster chromatin remodeling in its absence. HMO1 was evicted along with core histones during repair of DSBs, and chromatin remodeling events such as histone H2A phosphorylation and H3 eviction were faster in absence of HMO1. The facilitated chromatin remodeling in turn correlated with more efficient DNA resection and recruitment of repair proteins; for example, inward translocation of the DNA-end-binding protein Ku was faster in absence of HMO1. This chromatin stabilization requires the lysine-rich C-terminal extension of HMO1 as truncation of the HMO1 C-terminal tail phenocopies hmo1 deletion. Since this is reminiscent of the need for the basic C-terminal domain of mammalian histone H1 in chromatin compaction, we speculate that HMO1 promotes chromatin stability by DNA bending and compaction imposed by its lysine-rich domain and that it must be evicted along with core histones for efficient DSB repair.
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