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LCD1 : an essential gene involved in checkpoint control and regulation of the MEC1 signalling pathway in Saccharomyces cerevisiae
Author(s) -
Rouse John,
Jackson Stephen P.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.21.5801
Subject(s) - g2 m dna damage checkpoint , biology , dna damage , saccharomyces cerevisiae , dna repair , schizosaccharomyces pombe , dna replication , dna , microbiology and biotechnology , chek1 , cell cycle checkpoint , genetics , gene , cell cycle
We identified YDR499W as a Saccharomyces cerevisiae open reading frame with homology to several checkpoint proteins, including S.cerevisiae Rfc5p and Schizosaccharomyces pombe Rad26. Disruption of YDR499W (termed LCD1 ) results in lethality that is rescued by increasing cellular deoxyribonucleotide levels. Cells lacking LCD1 are very sensitive to a range of DNA‐damaging agents, including UV irradiation, and to the inhibition of DNA replication. LCD1 is necessary for the phosphorylation and activation of Rad53p in response to DNA damage or DNA replication blocks, and for Chk1p activation in response to DNA damage. LCD1 is also required for efficient DNA damage‐induced phosphorylation of Rad9p and for the association of Rad9p with the FHA2 domain of Rad53p after DNA damage. In addition, cells lacking LCD1 are completely defective in the G 1 /S and G 2 /M DNA damage checkpoints. Finally, we reveal that endogenous Mec1p co‐immunoprecipitates with Lcd1p both before and after treatment with DNA‐damaging agents. These results indicate that Lcd1p is a pivotal checkpoint regulator, involved in both the essential and checkpoint functions of the Mec1p pathway.