The nuclear actin-related protein Act3p/Arp4p of Saccharomyces cerevisiae is involved in transcription regulation of stress genes.
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, observed 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.
Görzer
Irene
I
Division of Molecular Genetics, Institute of Cancer Research, University of Vienna, A-1090 Vienna, Austria.
Schüller
Christoph
C
Heidenreich
Erich
E
Krupanska
Ludmila
L
Kuchler
Karl
K
Wintersberger
Ulrike
U
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005559:Formamides / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006918:Hydroxyurea / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000378:metabolism; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D000199:Actins; C088827:Arp4 protein, S cerevisiae; D004268:DNA-Binding Proteins; D005559:Formamides; D006360:Heat-Shock Proteins; C081935:MSN2 protein, S cerevisiae; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C031066:formamide; D006918:Hydroxyurea