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PMID:15132993

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Citation

Grossi, S, Puglisi, A, Dmitriev, PV, Lopes, M and Shore, D (2004) Pol12, the B subunit of DNA polymerase alpha, functions in both telomere capping and length regulation. Genes Dev. 18:992-1006

Abstract

The regulation of telomerase action, and its coordination with conventional DNA replication and chromosome end "capping," are still poorly understood. Here we describe a genetic screen in yeast for mutants with relaxed telomere length regulation, and the identification of Pol12, the B subunit of the DNA polymerase alpha (Pol1)-primase complex, as a new factor involved in this process. Unlike many POL1 and POL12 mutations, which also cause telomere elongation, the pol12-216 mutation described here does not lead to either reduced Pol1 function, increased telomeric single-stranded DNA, or a reduction in telomeric gene silencing. Instead, and again unlike mutations affecting POL1, pol12-216 is lethal in combination with a mutation in the telomere end-binding and capping protein Stn1. Significantly, Pol12 and Stn1 interact in both two-hybrid and biochemical assays, and their synthetic-lethal interaction appears to be caused, at least in part, by a loss of telomere capping. These data reveal a novel function for Pol12 and a new connection between DNA polymerase alpha and Stn1. We propose that Pol12, together with Stn1, plays a key role in linking telomerase action with the completion of lagging strand synthesis, and in a regulatory step required for telomere capping.

Links

PubMed PMC406290 Online version:10.1101/gad.300004

Keywords

Cell Cycle Proteins/metabolism; DNA Polymerase I/chemistry; DNA Polymerase I/genetics; DNA Polymerase I/metabolism; DNA Primase/chemistry; DNA Primase/genetics; DNA Primase/metabolism; Genes, Fungal; Mutation; Phenotype; Protein Subunits; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/metabolism; Telomere/metabolism; Telomere-Binding Proteins/metabolism

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