The nuclear actin-related protein Act3p/Arp4p of Saccharomyces cerevisiae is involved in transcription regulation of stress genes

The nuclear actin-related protein Act3p/Arp4p of Saccharomyces cerevisiae is involved in transcription regulation of stress genes
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DOI:
10.1046/j.1365-2958.2003.03759.x
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发表时间:
2003-11-01
影响因子:
3.6
通讯作者:
Wintersberger, U
Wintersberger, U
中科院分区:
生物学2区
文献类型:
--
作者:
Görzer, I;Schüller, C;Wintersberger, U

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对酿酒酵母(Saccharomycescerevisiae)细胞核肌动蛋白相关蛋白Act 3 p/Arp 4p进行了突变分析。选择用于取代的五个残基是肌动蛋白和Act 3 p/Arp 4p之间保守的氨基酸,其三级结构最可能类似于肌动蛋白。获得了两个温度敏感突变体,一个单点突变体和一个双点突变体,以及一个致死的双点突变体。这两个ts突变体是甲酰胺敏感的,这支持肌动蛋白的Act 3 p/Arp 4p的结构相关性,他们也对羟基脲和紫外线照射指向一个可能的作用,Act 3 p/Arp 4p在DNA复制和修复过敏。它们的“Ty抑制因子”(SPT)表型,以前在另一个Act 3 p/Arp 4p ts突变体中观察到,提示Act 3 p/Arp 4p参与转录调控。因此,全基因组表达谱分析揭示了许多基因的ts突变体中的转录失调,其中各种应激反应基因(其中许多需要Msn 2 p/Msn 4p进行诱导)的表达增加是最显著的结果。这为突变体增强对严重热应激和氧化应激的抗性提供了解释。因此,Act 3 p/Arp 4p在非胁迫条件下胁迫诱导基因的阻遏中起重要作用。
A mutational analysis of the essential nuclear actin-related protein of Saccharomyces cerevisiae, Act3p/Arp4p, was performed. The five residues chosen for substitution were amino acids conserved between actin and Act3p/Arp4p, the tertiary structure of which most probably resembles that of actin. Two thermosensitive (ts) mutants, a single and a double point mutant, and one lethal double point mutant were obtained. Both ts mutants were formamide-sensitive which supports a structural relatedness of Act3p/Arp4p to actin; they were also hypersensitive against hydroxyurea and ultraviolet irradiation pointing to a possible role of Act3p/Arp4p in DNA replication and repair. Their 'suppressor of Ty' (SPT) phenotype, ob-served with another ts mutant of Act3p/Arp4p before, suggested involvement of Act3p/Arp4p in transcription regulation. Accordingly, genome-wide expression profiling revealed misregulated transcription in a ts mutant of a number of genes, among which increased expression of various stress-responsive genes (many of them requiring Msn2p/Msn4p for induction) was the most salient result. This provides an explanation for the mutant's enhanced resistance to severe thermal and oxidative stress. Thus, Act3p/Arp4p takes an important part in the repression of stress-induced genes under non-stress conditions.