Copyright © 2002 Cell Press.
Molecular Cell, Vol 9, 1055-1065, May 2002

Article

Rad9 Phosphorylation Sites Couple Rad53 to the Saccharomyces cerevisiae DNA Damage Checkpoint

Marc F. Schwartz,1,2 Jimmy K. Duong,2 Zhaoxia Sun,2,3,5 Jon S. Morrow,2 Deepti Pradhan,2 and David F. Stern2

1Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510 USA

2Department of Pathology, Yale University School of Medicine, New Haven, CT 06510 USA

3Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06510 USA

u2217Corresponding author
David F. Stern
(203) 785-4832 (phone)
(203) 785-7467 (fax)
df.stern@yale.edu


Summary


Rad9 is required for the MEC1/TEL1-dependent activation of Saccharomyces cerevisiae DNA damage checkpoint pathways mediated by Rad53 and Chk1. DNA damage induces Rad9 phosphorylation, and Rad53 specifically associates with phosphorylated Rad9. We report here that multiple Mec1/Tel1 consensus [S/T]Q sites within Rad9 are phosphorylated in response to DNA damage. These Rad9 phosphorylation sites are selectively required for activation of the Rad53 branch of the checkpoint pathway. Consistent with the in vivo function in recruiting Rad53, Rad9 phosphopeptides are bound by Rad53 forkhead-associated (FHA) domains in vitro. These data suggest that functionally independent domains within Rad9 regulate Rad53 and Chk1, and support the model that FHA domain-mediated recognition of Rad9 phosphopeptides couples Rad53 to the DNA damage checkpoint pathway.

Footnotes

5Present address: Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.

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