Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Mol Cell. 2010 Feb 26;37(4):469-80. doi: 10.1016/j.molcel.2010.01.020.
Acetylation of lysine residues at the H3 N terminus is proposed to function in replication-coupled (RC) nucleosome assembly, a process critical for the inheritance of epigenetic information and maintenance of genome stability. However, the role of H3 N-terminal lysine acetylation and the corresponding lysine acetyltransferase (KAT) in RC nucleosome assembly are not known. Here we show that Gcn5, a KAT that functions in transcription, works in parallel with Rtt109, the H3 lysine 56 KAT, to promote RC nucleosome assembly. Cells lacking both Gcn5 and Rtt109 are highly sensitive to DNA damaging agents. Moreover, cells lacking GCN5 or those that express N-terminal H3 mutants are compromised for deposition of new H3 onto replicating DNA and also show reduced binding of H3 to CAF-1, a histone chaperone involved in RC nucleosome assembly. These results demonstrate that Gcn5 regulates RC nucleosome assembly, in part, by promoting H3 association with CAF-1 via H3 acetylation.
赖氨酸残基在 H3 N 末端的乙酰化被提议在复制偶联（RC）核小体组装中起作用，这是遗传表观遗传信息和维持基因组稳定性的关键过程。然而，H3 N 末端赖氨酸乙酰化及其相应的赖氨酸乙酰转移酶（KAT）在 RC 核小体组装中的作用尚不清楚。在这里，我们表明，在转录中起作用的 KAT Gcn5 与 H3 赖氨酸 56 KAT Rtt109 平行工作，以促进 RC 核小体组装。缺乏 Gcn5 和 Rtt109 的细胞对 DNA 损伤剂高度敏感。此外，缺乏 GCN5 或表达 N 末端 H3 突变体的细胞在将新的 H3 沉积到复制 DNA 上受到损害，并且也显示出 H3 与 CAF-1 的结合减少，CAF-1 是一种参与 RC 核小体组装的组蛋白伴侣。这些结果表明，Gcn5 通过促进 H3 通过 H3 乙酰化与 CAF-1 结合来调节 RC 核小体组装。
