Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage.
The DNA damage-responsive protein kinases ATM and ATR phosphorylate SQ/TQ motifs that lie in clusters in most of their in vivo targets. Budding yeast Esc4p contains a cluster of SQ/TQ motifs, suggesting that it might be a target of Mec1p/Tel1p (yeast ATR/ATM). Here it is reported that Esc4p is phosphorylated by Mec1p in response to DNA damage during DNA replication and that cells lacking Esc4p are hypersensitive to DNA damage specifically during S phase. Esc4p is not required for the intra-S-phase checkpoint but is essential for resumption of chromosome replication after DNA damage, and its role in promoting restart appears to be distinct from that of Rad53p. Mutation of Esc4p SQ/TQ motifs phosphorylated by Mec1p or mutation of the BRCT domains of Esc4p also renders cells unable to restart DNA replication after DNA damage and causes hypersensitivity to genotoxins. These results identify Esc4p as an important new S-phase-specific target of Mec1p.
Rouse
John
J
MRC Protein Phosphorylation Unit, Wellcome Trust Biocentre/Medical Sciences Institute, University of Dundee, Dundee DD1 5EH, UK. j.rouse@dundee.ac.uk
D043171:Chromosomal Instability; D015825:Chromosomes, Fungal / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D005810:Multigene Family; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004271:DNA, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C501265:RTT107 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases