Eukaryotic cells possess highly conserved signalling pathways – DNA damage checkpoints – that ensure that DNA damage caused by exogenous agents or normal physiological processes (e.g. DNA replication) is rapidly detected and repaired. On , Richard Blankley and David Lydall investigate the role that the adaptor protein Rad9p plays in the Saccharomyces cerevisiae DNA damage checkpoint. Rad9p couples Mec1p, a phosphoinositide-3-kinase (PI3K)-like kinase that is activated in response to most sorts of DNA damage, to two downstream effector kinases, Rad53p and Chk1p. Which effector kinase is activated depends on the type of DNA damage. To investigate the interaction between Radp9 and Chk1p, Blankley and Lydall devised a genetic screen for `separation of function' mutants – mutants defective in DNA damage responses that require Chk1p but not responses that require Rad53p. They report that the N-terminal domain of Radp9 is required for the activation of Chk1p but not Rad53p and speculate that similar domains exist in adaptor proteins from other eukaryotes.
