Saccharomyces telomeres consist of approximately 300 bp of C1-3A/TG1-3 DNA. Cells lacking the activity of the essential gene CDC13 display a cell cycle arrest mediated by the DNA damage sensing, RAD9 cell cycle checkpoint, presumably because they exhibit strand-specific loss of telomeric and telomere-adjacent DNA [Garvik, B., Carson, M. & Hartwell, L. (1995) Mol. Celi. Biol. 15,6128-6138]. Cdc13p expressed in Escherichia coli or overexpressed in yeast bound specifically to single-strand TG1-3 DNA. The specificity of binding displayed by Cdc13p in vitro indicates that in vivo it could bind to both the short, constitutive single-strand TG1-3 tails thought to be present at telomeres at most times in the cell cycle as well as to the long single-strand TG1-3 tails that are intermediates in telomere replication. Genes located near yeast telomeres are transcriptionally repressed, a phenomenon known as telomere position effect. Cells overexpressing a mutant form of Cdc13p had reduced telomere position effect at high temperatures. These data suggest that Cdc13p functions by binding directly to telomeric DNA, thereby limiting its accessibility to degradation and transcription as well as masking it from factors that detect damaged DNA.

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Journal Article | Research Support, U.S. Gov't, P.H.S.

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Lin JJ, Zakian VA

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