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Molecular and Cellular Biology, August 2000, p. 5888-5896, Vol. 20, No. 16
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Rfc5, in Cooperation with Rad24, Controls DNA
Damage Checkpoints throughout the Cell Cycle in
Saccharomyces cerevisiae
Takahiro
Naiki,
Toshiyasu
Shimomura,
Tae
Kondo,
Kunihiro
Matsumoto,* and
Katsunori
Sugimoto
Division of Biological Science, Graduate
School of Science, Nagoya University, Chikusa-ku, Nagoya 464-0814, Japan
Received 7 February 2000/Returned for modification 20 March
2000/Accepted 2 May 2000
RAD24 and RFC5 are required for DNA damage
checkpoint control in the budding yeast Saccharomyces
cerevisiae. Rad24 is structurally related to replication factor C
(RFC) subunits and associates with RFC subunits Rfc2, Rfc3,
Rfc4, and Rfc5. rad24
mutants are defective in all the
G1-, S-, and G2/M-phase DNA damage checkpoints, whereas the rfc5-1 mutant is impaired only in the S-phase
DNA damage checkpoint. Both the RFC subunits and Rad24 contain a
consensus sequence for nucleoside triphosphate (NTP) binding. To
determine whether the NTP-binding motif is important for Rad24
function, we mutated the conserved lysine115 residue in
this motif. The rad24-K115E mutation, which changes lysine
to glutamate, confers a complete loss-of-function phenotype, while the rad24-K115R mutation, which changes lysine to
arginine, shows no apparent phenotype. Although neither
rfc5-1 nor rad24-K115R single mutants are
defective in the G1- and G2/M-phase DNA damage checkpoints, rfc5-1 rad24-K115R double mutants become
defective in these checkpoints. Coimmunoprecipitation experiments
revealed that Rad24K115R fails to interact with the RFC
proteins in rfc5-1 mutants. Together, these results
indicate that RFC5, like RAD24, functions in
all the G1-, S- and G2/M-phase DNA damage
checkpoints and suggest that the interaction of Rad24 with the RFC
proteins is essential for DNA damage checkpoint control.
*
Corresponding author. Mailing address: Division of
Biological Science, Graduate School of Science, Nagoya University,
Chikusa-ku, Nagoya 464-8602, Japan. Phone: 81-52-789-2593. Fax:
81-52-789-2589. E-mail:
g44177a{at}nucc.cc.nagoya-u.ac.jp.

Present address: Tsukuba Research Institute, Banyu Pharmaceutical
Co., Ltd., Tsukuba 300-2611,
Japan.
Molecular and Cellular Biology, August 2000, p. 5888-5896, Vol. 20, No. 16
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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