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The rad3 gene of Schizosaccharomyces pombe is required for checkpoint pathways that respond to DNA damage and replication blocks. We report the complete rad3 gene sequence and show that rad3 is the homologue of Saccharomyces cerevisiae ESR1 (MEC1/SAD3) and Drosophila melanogaster mei-41 checkpoint genes. This establishes Rad3/Mec1 as the only conserved protein which is required for all the DNA structure checkpoints in both yeast model systems. Rad3 is an inessential member of the 'lipid kinase' subclass of kinases which includes the ATM protein defective in ataxia telangiectasia patients. Mutational analysis indicates that the kinase domain is required for Rad3 function, and immunoprecipitation of overexpressed Rad3 demonstrates an associated protein kinase activity. The previous observation that rad3 mutations can be rescued by a truncated clone lacking the kinase domain may be due to intragenic complementation. Consistent with this, biochemical data suggest that Rad3 exists in a complex containing multiple copies of Rad3. We have identified a novel human gene (ATR) whose product is closely related to Rad3/Esr1p/Mei-41. ATR can functionally complement esr1-1 radiation sensitivity in S. cerevisiae. Together, the structural conservation and functional complementation suggest strongly that the mechanisms underlying the DNA structure checkpoints are conserved throughout evolution.
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
June 1992,
Proceedings of the National Academy of Sciences of the United States of America,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
May 2014,
Molecular microbiology,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
April 1992,
The EMBO journal,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
November 1996,
Proceedings of the National Academy of Sciences of the United States of America,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
July 1998,
The Journal of biological chemistry,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
January 1999,
Biochimie,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
September 1992,
Gene,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
July 1998,
The Journal of biological chemistry,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
July 1999,
Genomics,
N J Bentley, and
D A Holtzman, and
G Flaggs, and
K S Keegan, and
A DeMaggio, and
J C Ford, and
M Hoekstra, and
A M Carr
April 2000,
Journal of cell science,
