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Vol. 10, Issue 6, 1985-1995, June 1999
§
*Cancer Research Laboratories, and Departments of
Eukaryotic cells actively block entry into mitosis in the presence
of DNA damage or incompletely replicated DNA. This response is mediated
by signal transduction cascades called cell cycle checkpoints. We show
here that the human checkpoint control protein hRAD9 physically
associates with two other checkpoint control proteins, hRAD1 and hHUS1.
Furthermore, hRAD1 and hHUS1 themselves interact, analogously to their
fission yeast homologues Rad1 and Hus1. We also show that hRAD9 is
present in multiple phosphorylation forms in vivo. These phosphorylated
forms are present in tissue culture cells that have not been exposed to
exogenous sources of DNA damage, but it remains possible that
endogenous damage or naturally occurring replication intermediates
cause the observed phosphorylation. Finally, we show that hRAD9 is a
nuclear protein, indicating that in this signal transduction pathway,
hRAD9 is physically proximal to the upstream (DNA damage) signal rather than to the downstream, cytoplasmic, cell cycle machinery.
Pathology, Oncology, and
§Biochemistry, Queen's University, Kingston, Ontario K7L
3N6, Canada
Corresponding author. E-mail address:
sd13{at}post.queensu.ca.
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