NDLI: The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast.

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The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast.

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The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hieter, P. Morrow, D. M. Brush, G. S. Kelly, T. J.
Description	Author Affiliation: Brush GS ( Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.);
Abstract	Replication protein A (RPA) is a highly conserved single-stranded DNA-binding protein, required for cellular DNA replication, repair, and recombination. In human cells, RPA is phosphorylated during the S and G2 phases of the cell cycle and also in response to ionizing or ultraviolet radiation. Saccharomyces cerevisiae exhibits a similar pattern of cell cycle-regulated RPA phosphorylation, and our studies indicate that the radiation-induced reactions occur in yeast as well. We have examined yeast RPA phosphorylation during the normal cell cycle and in response to environmental insult, and have demonstrated that the checkpoint gene MEC1 is required for the reaction under all conditions tested. Through examination of several checkpoint mutants, we have placed RPA phosphorylation in a novel pathway of the DNA damage response. MEC1 is similar in sequence to human ATM, the gene mutated in patients with ataxia-telangiectasia (A-T). A-T cells are deficient in multiple checkpoint pathways and are hypersensitive to killing by ionizing radiation. Because A-T cells exhibit a delay in ionizing radiation-induced RPA phosphorylation, our results indicate a functional similarity between MEC1 and ATM, and suggest that RPA phosphorylation is involved in a conserved eukaryotic DNA damage-response pathway defective in A-T.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	26
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA Replication DNA-Binding Proteins Metabolism Fungal Proteins Protein-Serine-Threonine Kinases Saccharomyces Cerevisiae Proteins Saccharomyces Cerevisiae Cytology Ataxia Telangiectasia Genetics Ataxia Telangiectasia Mutated Proteins Cell Cycle Radiation Effects Cell Cycle Proteins DNA Repair Genes, Fungal Genotype Intracellular Signaling Peptides And Proteins Models, Biological Phosphorylation Point Mutation Proteins Radiation, Ionizing Replication Protein A Tumor Suppressor Proteins Ultraviolet Rays Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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