A domain of Rad9 specifically required for activation of Chk1 in budding yeast.
The Rad9 protein is a key adaptor protein in Saccharomyces cerevisiae DNA damage checkpoint pathways. Its adaptor function is to link the activity of the Mec1 kinase to the activation of two parallel signalling pathways dependent on the Rad53 and Chk1 kinases. The mechanisms by which Rad9 interacts with, and activates, Rad53 are well understood. However, little was known about how Rad9 facilitates the activation of Chk1. We show here that the N-terminus of Rad9 is specifically important for phosphorylation and activation of the Chk1 kinase but not for the phosphorylation and activation of the Rad53 kinase. The Chk1 activation domain (CAD) of Rad9 is specifically important for signalling cell-cycle arrest after cdc13-1- and yku70Delta-induced telomere damage but not for tolerating ultraviolet-induced damage or inhibiting nuclease activity at telomeres. This work extends data showing that separable domains within the Rad9 adaptor protein allow it to activate two distinct kinase signalling pathways independently of each other.
Blankley
Richard T
RT
School of Biological Sciences, University of Manchester, G38 Stopford Building, Oxford Rd, Manchester, M13 9PT, UK.
Lydall
David
D
D000483:Alleles; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D004789:Enzyme Activation / Q000502:physiology; D017353:Gene Deletion; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development; D016415:Sequence Alignment; D015398:Signal Transduction
D018797:Cell Cycle Proteins; C069930:rad9 protein; D008741:Methyl Methanesulfonate; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1