Catalytic-site mutations in the MYST family histone acetyltransferase ESA1

被引:30
作者
Decker, Peter V. [1 ]
Yu, David Y. [1 ]
Iizuka, Masayoshi [1 ]
Qiu, Qifeng [1 ]
Smith, M. Mitchell [1 ,2 ]
机构
[1] Univ Virginia Hlth Syst, Dept Microbiol, Charlottesville, VA 22908 USA
[2] Univ Virginia Hlth Syst, Univ Virginia Canc Ctr, Charlottesville, VA 22908 USA
关键词
D O I
10.1534/genetics.107.080135
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Esa1 is the only essential histone acetyltransferase (HAT) in budding yeast. It is the catalytic subunit of at least two multiprotein complexes, NuA4 and Piccolo NuA4 (picNUA4), and its essential function is believed to be its catalytic HAT activity. To examine the role of Esa1 in DNA damage repair, we isolated via esa1 mutants with a range of hypersensitivities to the toposide camptothecin. Here we show that the sensitivity of these mutants to a variety of stresses is inversely proportional to their level of histone H4 acetylation, demonstrating the importance of Esa1 catalytic activity for resistance to genotoxic stress. Surprisingly, individual mutations in two residues directly involved in catalysis were not lethal even though the mutant enzymes appear catalytically inactive both in vivo and in, vitro. However, the double-point mutant is lethal, demonstrating that the essential function of Esa1 relies on residues within the catalytic pocket but not catalysis. We propose that the essential function of Esa1 may be to bind acetyl-CoA or lysine substrates and Positively regulate the activities of NuA4 and Piccolo NuA4.
引用
收藏
页码:1209 / 1220
页数:12
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