Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair

被引:436
作者
Bird, AW
Yu, DY
Pray-Grant, MG
Qiu, QF
Harmon, KE
Megee, PC
Grant, PA
Smith, MM
Christman, MF
机构
[1] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA
[2] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA
[3] Boston Univ, Med Ctr, Dept Genet & Genom, Boston, MA 02118 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature01035
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although the acetylation of histones has a well-documented regulatory role in transcription(1-4), its role in other chromosomal functions remains largely unexplored. Here we show that distinct patterns of histone H4 acetylation are essential in two separate pathways of double-strand break repair. A budding yeast strain with mutations in wild-type H4 acetylation sites shows defects in nonhomologous end joining repair and in a newly described pathway of replication-coupled repair. Both pathways require the ESA1 histone acetyl transferase (HAT), which is responsible for acetylating all H4 tail lysines, including ectopic lysines that restore repair capacity to a mutant H4 tail. Arp4, a protein that binds histone H4 tails and is part of the Esa1-containing NuA4 HAT complex, is recruited specifically to DNA double-strand breaks that are generated in vivo. The purified Esa1-Arp4 HAT complex acetylates linear nucleosomal arrays with far greater efficiency than circular arrays in vitro, indicating that it preferentially acetylates nucleosomes near a break site. Together, our data show that histone tail acetylation is required directly for DNA repair and suggest that a related human HAT complex may function similarly.
引用
收藏
页码:411 / 415
页数:6
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