NuA4 initiates dynamic histone H4 acetylation to promote high-fidelity sister chromatid recombination at postreplication gaps.
NuA4 initiates dynamic histone H4 acetylation to promote high-fidelity sister chromatid recombination at postreplication gaps.
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DOI：
10.1016/j.molcel.2014.07.007
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发表时间：
2014-09-18
期刊：
影响因子：
16
通讯作者：
Freudenreich, Catherine H.
中科院分区：
文献类型：
--
作者：
House, Nealia C. M.;Yang, Jiahui H.;Walsh, Stephen C.;Moy, Jonathan M.;Freudenreich, Catherine H.
CAG/CTG三核苷酸重复序列是不稳定的、脆弱的序列，它强烈定位核小体，但人们对这些或其他结构形成序列中防止基因组不稳定所需的染色质修饰知之甚少。我们发现，组蛋白H4乙酰化是维持CAG重复稳定性和促进GAP诱导的姐妹染色单体重组所必需的。在没有H4HATS NuA4和Hat1以及HDAC Sir2、Hos2、Hst1的情况下，CAG的扩张依赖于Rad52、Rad57和Rad5，因此是通过同源介导的复制后修复(PRR)事件引起的。在S期，需要H4K12和H4K16乙酰化来阻止RAD5依赖的CAG重复序列的扩张，而H4K16乙酰化在CAG重复序列上丰富。遗传学实验将RSC染色质重构体置于相同的PRR途径中，RSC2募集与H4K16乙酰化一致。在这里，我们利用一个重复的DNA序列，诱导内源性DNA损伤，以确定在复制后缺口修复过程中调节重组效率和保真度的组蛋白修饰。
CAG/CTG trinucleotide repeats are unstable, fragile sequences that strongly position nucleosomes, but little is known about chromatin modifications required to prevent genomic instability at these or other structure-forming sequences. We discovered that regulated histone H4 acetylation is required to maintain CAG repeat stability and promote gap-induced sister chromatid recombination. CAG expansions in the absence of H4 HATs NuA4 and Hat1 and HDACs Sir2, Hos2, Hst1 depended on Rad52, Rad57, and Rad5, and were therefore arising through homology-mediated post-replication repair (PRR) events. H4K12 and H4K16 acetylation were required to prevent Rad5-dependent CAG repeat expansions, and H4K16 acetylation was enriched at CAG repeats during S-phase. Genetic experiments placed the RSC chromatin remodeler in the same PRR pathway, and Rsc2 recruitment was coincident with H4K16 acetylation. Here we have utilized a repetitive DNA sequence that induces endogenous DNA damage to identify histone modifications that regulate recombination efficiency and fidelity during post-replication gap-repair.
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影响因子：
16
作者：
Minca EC;Kowalski D
通讯作者：
Kowalski D
影响因子：
4.8
作者：
Altaf, Mohammed;Auger, Andreanne;Cote, Jacques
通讯作者：
Cote, Jacques
影响因子：
16
作者：
Downs, JA;Allard, S;Côté, J
通讯作者：
Côté, J
DOI：
10.1073/pnas.1009409108
发表时间：
2011-02-15
影响因子：
11.1
作者：
Cherng, Nicole;Shishkin, Alexander A.;Mirkin, Sergei M.
通讯作者：
Mirkin, Sergei M.
DOI：
10.1073/pnas.95.12.6693
发表时间：
1998-06-09
影响因子：
11.1
作者：
Ma, XJ;Wu, JS;Grunstein, M
通讯作者：
Grunstein, M