Gómez Eliana B, Nugent Rebecca L, Laria Sebastián, Forsburg Susan L
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 90089-2910, USA.
Genetics. 2008 Jun;179(2):757-71. doi: 10.1534/genetics.107.085779. Epub 2008 May 27.
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 methyltransferase 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 hydroxyurea 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.
粟酒裂殖酵母Mst1是组蛋白乙酰转移酶MYST家族的成员,可能是酿酒酵母Esa1和人类Tip60(KAT5)的直系同源物。我们分离出了这个必需基因的一个温度敏感等位基因。mst1细胞在限制温度下表现出多效性表型。它们对多种DNA损伤剂和纺锤体毒物噻苯咪唑敏感。mst1的Rad22修复位点频率增加,表明存在内源性损伤。双杂交结果表明,Mst1与许多参与染色体完整性和着丝粒功能的蛋白质相互作用,包括甲基转移酶Skb1、重组介质Rad22(Sc Rad52)、染色质组装因子Hip1(Sc Hir1)以及与组蛋白去甲基酶家族相关的Msc1蛋白。mst1突变体对羟基脲的敏感性表明在HU阻滞恢复过程中存在缺陷。我们得出结论,Mst1在维持基因组稳定性和从DNA损伤中恢复方面发挥着重要作用。