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Abstract
Analysis of global gene expression in Saccharomyces cerevisiae by the serial analysis of gene expression technique has permitted the identification of at least 302 previously unidentified transcripts from nonannotated open reading frames (NORFs). Transcription of one of these, NORF5/HUG1 (hydroxyurea and UV and gamma radiation induced), is induced by DNA damage, and this induction requires MEC1, a homolog of the ataxia telangiectasia mutated (ATM) gene. DNA damage-specific induction of HUG1, which is independent of the cell cycle stage, is due to the alleviation of repression by the Crt1p-Ssn6p-Tup1p complex. Overexpression of HUG1 is lethal in combination with a mec1 mutation in the presence of DNA damage or replication arrest, whereas a deletion of HUG1 rescues the lethality due to a mec1 null allele. HUG1 is the first example of a NORF with important biological functional properties and defines a novel component of the MEC1checkpoint pathway.
ACKNOWLEDGMENTS
We gratefully acknowledge the gifts of strains and plasmids, suggestions, or support from A. Basrai, D. Bassett, J. Boeke, G. Brush, C. Connelly, S. Elledge, K. Gupta, the L. Hartwell laboratory, M. Huang, K. Hyland, M. Johnston, M. Kenna, I. Kirsch, R. Kitagawa, D. Koshland, R. Krishnan, S. Michaelis, D. Morrow, P. Paddison, R. Rothstein, R. Skibbens, F. Spencer, B. Vogelstein, T. Weinert, J. Zhang, X. Zhao, and our laboratory members. We thank J. Vogelstein for analysis of NORF data; S. Dwight, T. Roe, C. Ball, A. Malekian, and M. Cherry of the Stanford Genome Database for annotation of new ORFs based on SAGE analysis; J. Flook for assistance with flow cytometry; and L. Dillehay for assistance with gamma irradiation. M.A.B. thanks C. Greider for constant support and M. Huang and P. Paddison for valuable suggestions.
K.W.K. received research funding from Genzyme Molecular Oncology (Genzyme). P.H. was supported by grants NIH CA16519 and NIH HD24605.