PMID:16598261

Citation	Miller, KM, Rog, O and Cooper, JP (2006) Semi-conservative DNA replication through telomeres requires Taz1. Nature 440:824-8
Abstract	Telomere replication is achieved through the combined action of the conventional DNA replication machinery and the reverse transcriptase, telomerase. Telomere-binding proteins have crucial roles in controlling telomerase activity; however, little is known about their role in controlling semi-conservative replication, which synthesizes the bulk of telomeric DNA. Telomere repeats in the fission yeast Schizosaccharomyces pombe are bound by Taz1, a regulator of diverse telomere functions. It is generally assumed that telomere-binding proteins impede replication fork progression. Here we show that, on the contrary, Taz1 is crucial for efficient replication fork progression through the telomere. Using two-dimensional gel electrophoresis, we find that loss of Taz1 leads to stalled replication forks at telomeres and internally placed telomere sequences, regardless of whether the telomeric G-rich strand is replicated by leading- or lagging-strand synthesis. In contrast, the Taz1-interacting protein Rap1 is dispensable for efficient telomeric fork progression. Upon loss of telomerase, taz1Delta telomeres are lost precipitously, suggesting that maintenance of taz1Delta telomere repeats cannot be sustained through semi-conservative replication. As the human telomere proteins TRF1 and TRF2 are Taz1 orthologues, we predict that one or both of the human TRFs may orchestrate fork passage through human telomeres. Stalled forks at dysfunctional human telomeres are likely to accelerate the genomic instability that drives tumorigenesis.
Links	PubMed Online version:10.1038/nature04638
Keywords	DNA Replication; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Kinetics; Schizosaccharomyces/genetics; Schizosaccharomyces/metabolism; Schizosaccharomyces pombe Proteins/genetics; Schizosaccharomyces pombe Proteins/metabolism; Telomerase/deficiency; Telomerase/genetics; Telomerase/metabolism; Telomere/genetics; Telomere/metabolism; Telomere-Binding Proteins/deficiency; Telomere-Binding Proteins/genetics; Telomere-Binding Proteins/metabolism; Templates, Genetic
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
SCHPO:TAZ1	involved_in	GO:1902990: mitotic telomere maintenance via semi-conservative replication	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

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