保守的组蛋白伴侣 Spt6 强烈需要 DNA 复制和基因组稳定性。
The conserved histone chaperone Spt6 is strongly required for DNA replication and genome stability.
机构信息
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Cell Rep. 2023 Mar 28;42(3):112264. doi: 10.1016/j.celrep.2023.112264. Epub 2023 Mar 15.
Histone chaperones are an important class of proteins that regulate chromatin accessibility for DNA-templated processes. Spt6 is a conserved histone chaperone and key regulator of transcription and chromatin structure. However, its functions outside of these roles have been little explored. In this work, we demonstrate a requirement for S. cerevisiae Spt6 in DNA replication and, more broadly, as a regulator of genome stability. Depletion or mutation of Spt6 impairs DNA replication in vivo. Additionally, spt6 mutants are sensitive to DNA replication stress-inducing agents. Interestingly, this sensitivity is independent of the association of Spt6 with RNA polymerase II (RNAPII), suggesting that spt6 mutants have a transcription-independent impairment of DNA replication. Specifically, genomic studies reveal that spt6 mutants have decreased loading of the MCM replicative helicase at replication origins, suggesting that Spt6 promotes origin licensing. Our results identify Spt6 as a regulator of genome stability, at least in part through a role in DNA replication.
组蛋白伴侣是一类重要的蛋白质，它们可以调节 DNA 模板过程的染色质可及性。Spt6 是一种保守的组蛋白伴侣，也是转录和染色质结构的关键调节剂。然而，其在这些角色之外的功能尚未得到充分探索。在这项工作中，我们证明了酿酒酵母 Spt6 在 DNA 复制中的必要性，更广泛地说，它是基因组稳定性的调节剂。Spt6 的耗尽或突变会损害体内的 DNA 复制。此外，spt6 突变体对 DNA 复制应激诱导剂敏感。有趣的是，这种敏感性与 Spt6 与 RNA 聚合酶 II（RNAPII）的关联无关，这表明 spt6 突变体在转录上存在独立于 DNA 复制的缺陷。具体来说，基因组研究表明，spt6 突变体在复制起始点处的 MCM 复制解旋酶的加载减少，这表明 Spt6 促进了起始点许可。我们的结果表明，Spt6 是基因组稳定性的调节剂，至少部分是通过在 DNA 复制中的作用。
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