Open AccessRole of the casein kinase I isoform, Hrr25, and the cell cycle-regulatory transcription factor, SBF, in the transcriptional response to DNA damage in Saccharomyces cerevisiae
Author(s) -
Yuen Ho,
Stephen W. Mason,
Ryûji Kobayashi,
Merl F. Hoekstra,
Brenda Andrews
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.2.581
Subject(s) - biology , methyl methanesulfonate , dna damage , dna repair , transcription factor , protein kinase a , microbiology and biotechnology , kinase , transcription (linguistics) , mutant , dna , gene , biochemistry , linguistics , philosophy
In the budding yeast,Saccharomyces cerevisiae , DNA damage or ribonucleotide depletion causes the transcriptional induction of an array of genes with known or putative roles in DNA repair. The ATM-like kinase, Mec1, and the serine/threonine protein kinases, Rad53 and Dun1, are required for this transcriptional response. In this paper, we provide evidence suggesting that another kinase, Hrr25, is also involved in the transcriptional response to DNA damage through its interaction with the transcription factor, Swi6. The Swi6 protein interacts with Swi4 to form the SBF complex and with Mbp1 to form the MBF complex. SBF and MBF are required for the G1 -specific expression of G1 cyclins and genes required for S-phase. We show that Swi6 associates with and is phosphorylated by Hrr25in vitro . We find thatswi4 ,swi6 , andhrr25 mutants, but notmbp1 mutants, are sensitive to hydroxyurea and the DNA-damaging agent methyl methanesulfonate and are defective in the transcriptional induction of a subset of DNA damage-inducible genes. Both the sensitivity ofswi6 mutants to methyl methanesulfonate and hydroxyurea and the transcriptional defect ofhrr25 mutants are rescued by overexpression ofSWI4 , implicating the SBF complex in the Hrr25/Swi6-dependent response to DNA damage.