Molecular and Cellular Biology, February 2001, p. 755-764, Vol. 21, No. 3
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.3.755-764.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Division of Biological Science, Graduate School of Science, Nagoya University,1 and CREST, Japan Science and Technology Corporation,2 Chikusa-ku, Nagoya 464-0814, Japan
Received 14 August 2000/Returned for modification 29 September 2000/Accepted 7 November 2000
In eukaryotes, the ATM and ATR family proteins play a critical role
in the DNA damage and replication checkpoint controls. These proteins
are characterized by a kinase domain related to the
phosphatidylinositol 3-kinase, but they have the ability to phosphorylate proteins. In budding yeast, the ATR family protein Mec1/Esr1 is essential for checkpoint responses and cell growth. We
have isolated the PIE1 gene in a two-hybrid screen for
proteins that interact with Mec1, and we show that Pie1 interacts
physically with Mec1 in vivo. Like MEC1, PIE1
is essential for cell growth, and deletion of the PIE1 gene
causes defects in the DNA damage and replication block checkpoints
similar to those observed in mec1
mutants. Rad53
hyperphosphorylation following DNA damage and replication block is
also decreased in pie1
cells, as in mec1
cells. Pie1 has a limited homology to fission yeast Rad26, which forms
a complex with the ATR family protein Rad3. Mutation of the region in
Pie1 homologous to Rad26 results in a phenotype similar to that of the
pie1
mutation. Mec1 protein kinase activity appears to
be essential for checkpoint responses and cell growth. However, Mec1
kinase activity is unaffected by the pie1
mutation, suggesting that Pie1 regulates some essential function other than Mec1
kinase activity. Thus, Pie1 is structurally and functionally related to
Rad26 and interacts with Mec1 to control checkpoints and cell proliferation.
Present address: Kyowa Hakko Kogyo Co. Ltd., Machida-shi, Tokyo
194-8533, Japan.
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