Remodelling the Rad9 checkpoint complex: preparing Rad53 for action.
DNA damage checkpoints are signal transduction pathways that are activated after genotoxic insults to protect genomic integrity. The Rad9 protein functions in the DNA damage checkpoint pathway in Saccharomyces cerevisiae and is essential for the Mec1-dependent activation of the effector kinase Rad53. We recently described the purification of two soluble distinct Rad9 complexes. The large 850 kDa complex consists of hypophosphorylated Rad9 and the chaperone proteins Ssa1/2. This complex is found both in undamaged cells as well as in cells treated with DNA damaging agents. The smaller 560 kDa complex contains hyperphosphorylated Rad9, Ssa1/2 and, in addition, Rad53. This complex forms only in cells with compromised DNA integrity. Once bound to the smaller complex, Rad53 can be activated by in trans autophosphorylation. Here, we propose a model in which the large Rad9 complex is remodelled after a genomic insult by chaperone activity to a smaller Rad53 activating complex.
van den Bosch
Michael
M
Department of Biochemistry and National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland.
Lowndes
Noel F
NF
D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D008958:Models, Molecular; D016296:Mutagenesis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000502:physiology
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; C542288:SSA2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae