Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis.
Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis.
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DOI：
10.1038/ncb1903
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发表时间：
2009-08
影响因子：
21.3
通讯作者：
Gunjan, Akash
中科院分区：
文献类型：
--
作者：
Singh, Rakesh Kumar;Kabbaj, Marie-Helene Miquel;Paik, Johanna;Gunjan, Akash
组蛋白水平受到严格调控，以防止有害影响，如基因组不稳定性和对DNA损伤剂的超敏反应，这是由于当DNA复制减慢或停止时这些高碱性蛋白质的积累。虽然染色体组蛋白是稳定的，但过量的（非染色质结合的）组蛋白在酿酒酵母中以Rad53激酶依赖性方式快速降解。在这里，我们表明，过量的组蛋白与Rad53在体内，似乎经历的修改，如酪氨酸磷酸化和多泛素化，之前，他们的蛋白酶体的蛋白水解。我们已经确定组蛋白H3的酪氨酸99残基对于该组蛋白的有效遍在化和降解至关重要。我们还确定了E2蛋白Ubc4和Ubc5，以及E3泛素连接酶Tom1，作为参与过量组蛋白泛素化的酶。调节组蛋白水解对染色质表观遗传标记的维持、基因组稳定性和精子DNA的包装具有重要意义。
Histone levels are tightly regulated to prevent harmful effects such as genomic instability and hypersensitivity to DNA damaging agents due to the accumulation of these highly basic proteins when DNA replication slows down or stops. Although chromosomal histones are stable, excess (non-chromatin bound) histones are rapidly degraded in a Rad53 kinase dependent manner in Saccharomyces cerevisiae. Here we demonstrate that excess histones associate with Rad53 in vivo, appear to undergo modifications such as tyrosine phosphorylation and polyubiquitylation, before their proteolysis by the proteasome. We have identified the tyrosine 99 residue of histone H3 as being critical for the efficient ubiquitylation and degradation of this histone. We have also identified the E2 proteins Ubc4 and Ubc5, as well as the E3 ubiquitin ligase Tom1, as enzymes involved in the ubiquitylation of excess histones. Regulated histone proteolysis has major implications for the maintenance of epigenetic marks on chromatin, genomic stability and the packaging of sperm DNA.
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