Abstract
Activation of phospholipase C-dependent inositol polyphosphate signaling pathways generates distinct messengers derived from inositol 1,4,5-trisphosphate that control gene expression and mRNA export. Here we report the regulation of telomere length by production of a diphosphorylinositol tetrakisphosphate, PP-IP4, synthesized by the KCS1 gene product. Loss of PP-IP4 production results in lengthening of telomeres, whereas overproduction leads to their shortening. This effect requires the presence of Tel1, the yeast homologue of ATM, the protein mutated in the human disease ataxia telangiectasia. Our data provide in vivo evidence of a regulatory link between inositol polyphosphate signaling and the checkpoint kinase family and describe a third nuclear process modulated by phospholipase C activation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Ataxia Telangiectasia Mutated Proteins
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Biological Transport
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Blotting, Southern
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Cell Cycle Proteins / metabolism
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Gene Expression Regulation
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Genetic Complementation Test
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Hydrolysis
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Inositol Phosphates / metabolism*
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Models, Biological
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Mutation
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Open Reading Frames
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Phosphorylation
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Phosphotransferases (Phosphate Group Acceptor)
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Plasmids / metabolism
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Protein Serine-Threonine Kinases / metabolism
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RNA, Messenger / metabolism
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / biosynthesis
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Saccharomyces cerevisiae Proteins / physiology*
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Signal Transduction*
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Telomere / ultrastructure*
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Time Factors
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Tumor Suppressor Proteins / metabolism
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Type C Phospholipases / chemistry
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Type C Phospholipases / metabolism
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Inositol Phosphates
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RNA, Messenger
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Saccharomyces cerevisiae Proteins
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Tumor Suppressor Proteins
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases
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Phosphotransferases (Phosphate Group Acceptor)
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KCS1 protein, S cerevisiae
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Type C Phospholipases