Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination.
Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination.
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酵母 Bromodomain 因子 1 及其人类同源物 TAF1 在促进同源重组中发挥保守作用
DOI：
10.1002/advs.202100753
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Peng H;Zhang S;Peng Y;Zhu S;Zhao X;Zhao X;Yang S;Liu G;Dong Y;Gan X;Li Q;Zhang X;Pei H;Chen X
组蛋白乙酰化是一种关键的组蛋白翻译后修饰，影响染色质的结构、动力学和功能。溴域（BRD）蛋白是乙酰赖氨酸的读取器，位于组蛋白乙酰化信号网络的中心。它们如何调节DNA修复和基因组稳定性仍然知之甚少。本文报道了酵母溴域因子1 （Bdf1）及其人类对应物TAF1的保守功能，通过同源重组（HR）促进DNA双链断裂修复。酵母BDF1或人TAF1的缺失或其brd的破坏都会损害DNA末端切除、复制蛋白A （RPA）和Rad51的装载以及HR修复，从而导致基因组不稳定和对DNA损伤的超敏反应。从机制上讲，研究表明Bdf1通过BRD基序优先结合DNA损伤诱导的组蛋白H4乙酰化（H4Ac），导致其染色质募集。同时，Bdf1与RPA发生物理相互作用，这种相互作用促进了RPA在染色质环境下的装载和随后的HR修复。同样，TAF1也与H4Ac或RPA相互作用。因此，Bdf1和TAF1似乎共享一个保守的机制，将HR修复与染色质乙酰化联系起来，以保持基因组的完整性。溴结构域（BRD）蛋白，乙酰赖氨酸的读取器，如何调节DNA修复和基因组稳定性仍不完全清楚。本研究表明，酵母溴域因子1 （Bdf1）及其人类对应物TAF1的保守功能通过物理上促进复制蛋白a （RPA）加载在断裂端分散的组蛋白的ssDNA上，通过同源重组途径促进DNA双链断裂修复。
Histone acetylation is a key histone post‐translational modification that shapes chromatin structure, dynamics, and function. Bromodomain (BRD) proteins, the readers of acetyl‐lysines, are located in the center of the histone acetylation‐signaling network. How they regulate DNA repair and genome stability remains poorly understood. Here, a conserved function of the yeast Bromodomain Factor 1 (Bdf1) and its human counterpart TAF1 is reported in promoting DNA double‐stranded break repair by homologous recombination (HR). Depletion of either yeast BDF1 or human TAF1, or disruption of their BRDs impairs DNA end resection, Replication Protein A (RPA) and Rad51 loading, and HR repair, causing genome instability and hypersensitivity to DNA damage. Mechanistically, it is shown that Bdf1 preferentially binds the DNA damage‐induced histone H4 acetylation (H4Ac) via the BRD motifs, leading to its chromatin recruitment. Meanwhile, Bdf1 physically interacts with RPA, and this interaction facilitates RPA loading in the chromatin context and the subsequent HR repair. Similarly, TAF1 also interacts with H4Ac or RPA. Thus, Bdf1 and TAF1 appear to share a conserved mechanism in linking the HR repair to chromatin acetylation in preserving genome integrity. How the bromodomain (BRD) proteins, readers of acetyl‐lysines, regulate DNA repair and genome stability remains partially understood. Here, a conserved function of the yeast Bromodomain Factor 1 (Bdf1) and its human counterpart TAF1 is shown in promoting DNA double‐stranded break repair by the homologous recombination pathway via physically facilitating Replication Protein A (RPA) loading on ssDNA with dispersed histones at break ends.
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影响因子：
3.7
作者：
Gibb B;Ye LF;Gergoudis SC;Kwon Y;Niu H;Sung P;Greene EC
通讯作者：
Greene EC
DOI：
10.1126/science.1135862
发表时间：
2007-02-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
Llorente, Bertrand
DOI：
10.1073/pnas.1806513115
发表时间：
2018-10-02
影响因子：
11.1
作者：
Cheng, Xue;Jobin-Robitaille, Olivier;Cote, Jacques
通讯作者：
Cote, Jacques