Role 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

Abstract

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 serine͞threonine 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 G 1 -specific expression of G 1 cyclins and genes required for S-phase. We show that Swi6 associates with and is phosphorylated by Hrr25 in vitro. We find that swi4, swi6, and hrr25 mutants, but not mbp1 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 of swi6 mutants to methyl methanesulfonate and hydroxyurea and the transcriptional defect of hrr25 mutants are rescued by overexpression of SWI4, implicating the SBF complex in the Hrr25͞Swi6-dependent response to DNA damage.

Damage-mediated Phosphorylation of Human p53 Threonine 18 through a Cascade Mediated by a Casein 1-like Kinase

“…Yeast HRR25 mutants are defective in the transcriptional induction of a subset of DNA damage-inducible genes that require Swi6, a transcription factor phosphorylated by Hrr25 in vitro (39). Murine CK1 phosphorylates several residues at the N terminus of mouse p53 (23,24), but these residues are not completely conserved in human p53, and our attempts to phosphorylate the N terminus of unmodified human p53 with recombinant CK1-␦ were unsuccessful (Fig.…”

Phosphorylation and functions of the RNA polymerase II CTD

“…Interestingly, the binding domains of three of these proteins bind best to Ser2,5P repeats, whereas the binding domain of Ssd1 binds equally well to Ser2,5P and Ser2P repeats ; the functional significance of these specificities have yet to be explored in vivo. Of this group, the protein with perhaps the most novel implications is Hrr25, a protein kinase involved in response to DNA damage (Ho et al 1997). The selective binding of Hrr25 to 2,5P repeats suggests a role in DNA damage responses for RNAPII carrying repeats phosphorylated in this pattern.…”

A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae

“…The KTI14 gene was found to be allelic to HRR25 (Mehlgarten and Schaffrath 2003), which encodes a casein kinase homolog involved in diverse cellular processes, for example, DNA repair, vesicular trafficking, calcineurin signaling, ribosome maturation, and chromosome segregation (Hoekstra et al 1991;DeMaggio et al 1992;Ho et al 1997;Murakami et al 1999;Kafadar et al 2003;Petronczki et al 2006;Schafer et al 2006 U are shown in bold. The strains used were wt (UMY2893), sit4D (UMY3210), sap4D sap155D (UMY3214), sap185D (UMY3232), sap190D (UMY3204), sap185D sap190D (UMY3262), trm9D (UMY3024), and kti14-1 (UMY3273).…”