Schizosaccharomyces pombe histone acetyltransferase Mst1 (KAT5) is an essential protein required for damage response and chromosome segregation

Schizosaccharomyces pombe histone acetyltransferase Mst1 (KAT5) is an essential protein required for damage response and chromosome segregation
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DOI:
10.1534/genetics.107.085779
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发表时间:
2008-06-01
期刊:
影响因子:
3.3
通讯作者:
Forsburg, Susan L.
Forsburg, Susan L.
中科院分区:
生物学2区
文献类型:
--
作者:
Gomez, Eliana B.;Nugent, Rebecca L.;Forsburg, Susan L.

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粟酒裂殖酵母Mst 1是组蛋白乙酰转移酶MYST家族的成员,并且可能是酿酒酵母Esa 1和人Tip 60(KAT 5)的直系同源物。我们已经分离出这个必需基因的温度敏感等位基因。MST 1细胞在限制性温度下表现出多效性表型。它们对多种DNA损伤剂和纺锤体毒素噻苯咪唑敏感。mst 1具有增加的Rad22修复灶频率,表明内源性损伤。双杂交结果表明,Mst 1相互作用与染色体的完整性和着丝粒功能,包括甲基转移酶Skb 1,重组介体Rad22(Sc Rad52),染色质组装因子Hip 1(Sc Hir1),和Msc 1蛋白相关的组蛋白去甲基化酶家族的蛋白质。mst 1突变体对羟基脲的敏感性表明HU停滞后的恢复缺陷。我们的结论是,Mst 1在维持基因组稳定性和恢复DNA损伤中起着至关重要的作用。
Schizosaccharomyces pombe Mst1 is a member of the MYST family of histone acetyltransferases and is the likely ortholog of Saccharomyces cerevisiae Esa1 and human Tip60 (KAT5). We have isolated a temperature-sensitive allele of this essential gene. mst1 cells show a pleiotropic phenotype at the restrictive temperature. They are sensitive to a variety of DNA-damaging agents and to the spindle poison thiabendazole. mst1 has an increased frequency of Rad22 repair foci, suggesting endogenous damage. Two-hybrid results show that Mst1 interacts with a number of proteins involved in chromosome integrity and centromere function, including the m ethyl transferase Skb1, the recombination mediator Rad22 (Sc Rad52), the chromatin assembly factor Hip1 (Sc Hir1), and the Msc1 protein related to a family of histone demethylases. mst1 mutant sensitivity to bydroxyurea suggests a defect in recovery following HU arrest. We conclude that Mst1 plays essential roles in maintenance of genome stability and recovery from DNA damage.