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Science 19 January 1996:
Vol. 271. no. 5247, pp. 357 - 360
DOI: 10.1126/science.271.5247.357
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Reports

Regulation of RAD53 by the ATM-Like Kinases MEC1 and TEL1 in Yeast Cell Cycle Checkpoint Pathways

Yolanda Sanchez,  Brian A. Desany,  William J. Jones,  Qinghua Liu,  Bin Wang,  Stephen J. Elledge (1)

Mutants of the Saccharomyces cerevisiae ataxia telangiectasia mutated (ATM) homolog MEC1/SAD3/ESR1 were identified that could live only if the RAD53/SAD1 checkpoint kinase was overproduced. MEC1 and a structurally related gene, TEL1, have overlapping functions in response to DNA damage and replication blocks that in mutants can be provided by overproduction of RAD53. Both MEC1 and TEL1 were found to control phosphorylation of Rad53p in response to DNA damage. These results indicate that RAD53 is a signal transducer in the DNA damage and replication checkpoint pathways and functions downstream of two members of the ATM lipid kinase family. Because several members of this pathway are conserved among eukaryotes, it is likely that a RAD53-related kinase will function downstream of the human ATM gene product and play an important role in the mammalian response to DNA damage.


Verna and Mars McLean Department of Biochemistry, Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
(1) To whom correspondence should be addressed.


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Genes & Dev. 16, 3236-3252
   Abstract »    Full Text »    PDF »
An N-terminal domain of Dbf4p mediates interaction with both origin recognition complex (ORC) and Rad53p and can deregulate late origin firing.
B. P. Duncker, K. Shimada, M. Tsai-Pflugfelder, P. Pasero, and S. M. Gasser (2002)
PNAS 99, 16087-16092
   Abstract »    Full Text »    PDF »
NuA4 Subunit Yng2 Function in Intra-S-Phase DNA Damage Response.
J. S. Choy and S. J. Kron (2002)
Mol. Cell. Biol. 22, 8215-8225
   Abstract »    Full Text »    PDF »
Rare Variants of ATM and Risk for Hodgkin's Disease and Radiation-associated Breast Cancers.
K. Offit, S. Gilad, S. Paglin, P. Kolachana, L. C. Roisman, K. Nafa, V. Yeugelewitz, M. Gonzales, M. Robson, D. McDermott, et al. (2002)
Clin. Cancer Res. 8, 3813-3819
   Abstract »    Full Text »    PDF »
A dominant-negative MEC3 mutant uncovers new functions for the Rad17 complex and Tel1.
M. Giannattasio, E. Sommariva, R. Vercillo, F. Lippi-Boncambi, G. Liberi, M. Foiani, P. Plevani, and M. Muzi-Falconi (2002)
PNAS 99, 12997-13002
   Abstract »    Full Text »    PDF »
Chk2 Activation and Phosphorylation-Dependent Oligomerization.
X. Xu, L. M. Tsvetkov, and D. F. Stern (2002)
Mol. Cell. Biol. 22, 4419-4432
   Abstract »    Full Text »    PDF »


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