A role for Gcn5 in replication-coupled nucleosome assembly.

A role for Gcn5 in replication-coupled nucleosome assembly.
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DOI:
10.1016/j.molcel.2010.01.020
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发表时间:
2010-02-26
期刊:
影响因子:
16
通讯作者:
Zhang Z
Zhang Z
中科院分区:
生物学1区
文献类型:
--
作者:
Burgess RJ;Zhou H;Han J;Zhang Z

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H3 N-末端赖氨酸残基的乙酰化被认为在复制偶联(RC)核小体组装中起作用,这是一个对表观遗传信息的遗传和基因组稳定性的维持至关重要的过程。然而,在RC核小体组装中H3 N-末端赖氨酸乙酰化和相应的赖氨酸乙酰转移酶(KAT)的作用尚不清楚。在这里,我们表明,Gcn 5,一个KAT与基因转录中的作用进行了充分的研究,平行的功能与Rtt 109,H3赖氨酸56 KAT,以促进RC核小体组装。缺乏Gcn 5和Rtt 109的细胞对DNA损伤剂高度敏感。此外,缺乏GCN 5或表达在H3 N-末端具有突变的H3突变体的细胞导致新H3在复制DNA上的沉积受损以及H3与CAF-1(一种参与RC核小体组装的组蛋白伴侣)的结合减少。这些结果表明,Gcn 5调节RC核小体组装,部分地通过促进H3与CAF-1通过H3乙酰化的关联。
Acetylation of lysine residues at the H3 N-terminus is proposed to have a role 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 with a well-studied role in gene transcription, functions 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 expressing an H3 mutant with mutations at the H3 N-terminus result in compromised deposition of new H3 onto replicating DNA and a reduction in the binding of H3 with CAF-1, a histone chaperone involved in RC nucleosome assembly. These results demonstrate that Gcn5 regulates RC nucleosome assembly, in part, through promoting the association of H3 with CAF-1 via H3 acetylation.
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