Histone acetyltransferase 1 is dispensable for replication-coupled chromatin assembly but contributes to recover DNA damages created following replication blockage in vertebrate cells
Histone acetyltransferase 1 is dispensable for replication-coupled chromatin assembly but contributes to recover DNA damages created following replication blockage in vertebrate cells
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DOI：
10.1016/j.bbrc.2006.05.079
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发表时间：
2006-07-14
影响因子：
3.1
通讯作者：
Nakayama, Tatsuo
中科院分区：
文献类型：
--
作者：
Barman, Hirak Kumar;Takami, Yasunari;Nakayama, Tatsuo
组蛋白乙酰转移酶1（HAT 1）参与新合成的组蛋白H4的赖氨酸-5和赖氨酸-12的双乙酰化，其生物学意义尚不清楚。为了研究HAT I在体内的作用，我们产生了HAT 1缺陷型DT 40克隆（HAT 1（-/-））。HAT 1（-/-）细胞表现出细胞质和染色质组蛋白H4的Lys-5和Lys-12的双乙酰化水平以及Lys-5的乙酰化水平分别大大降低。体外核小体组装实验和体内MNase消化实验表明，HAT 1和历史H4的Lys-5和Lys-12的双乙酰化是复制偶联染色质组装的关键。HAT 1（-/-）细胞有轻度生长缺陷，对甲磺酸甲酯和喜树碱敏感，这两种药物可阻断复制，造成DNA双链断裂。这种高度敏感性与延长的晚S/G2期有关。这些结果表明，HAT 1参与恢复复制块介导的DNA损伤，可能通过染色质调制的基础上乙酰化的历史H4的赖氨酸-5和赖氨酸-12。(c)2006爱思唯尔公司All rights reserved.
Histoneacetyltransferase 1 (HAT1) is implicated for diacetylation of Lys-5 and Lys-12 of newly synthesized histo tie H4, the biological significance of which remains unclear. To investigate the in vivo role of HAT I, we generated HAT1-deficient DT40 clone (HAT1(-/-)). HAT1(-/-) cells exhibited greatly reduced diacetylation levels of Lys-5 and Lys-12, and acetylation level of Lys-5 of cytosolic and chromatin histones H4, respectively. The in vitro nucleosome assembly assay and in vivo MNase digestion assay revealed that HAT1 and diacetylation of Lys-5 and Lys-12 of historic H4 are dispensable for replication-coupled chromatin assembly. HAT1(-/-) cells had mild growth defect, conferring sensitivities to methyl methanesulfonate and camptothecin that enforce replication blocks creating DNA double strand breaks. Such heightened sensitivities were associated with prolonged late-S/G2 phase. These results indicate that HAT1 participates in recovering replication block-mediated DNA damages, probably through chromatin modulation based on acetylation of Lys-5 and Lys-12 of historic H4. (c) 2006 Elsevier Inc. All rights reserved.