Abstract
Telomeres are specialized nucleoprotein structures that stabilize the ends of linear eukaryotic chromosomes. In mammalian cells, abrogation of telomeric repeat binding factor TRF2 or DNA-dependent protein kinase (DNA-PK) activity causes end-to-end chromosomal fusion, thus establishing an essential role for these proteins in telomere function. Here we show that TRF2-mediated end-capping occurs after telomere replication. The postreplicative requirement for TRF2 and DNA-PKcs, the catalytic subunit of DNA-PK, is confined to only half of the telomeres, namely, those that were produced by leading-strand DNA synthesis. These results demonstrate a crucial difference in postreplicative processing of telomeres that is linked to their mode of replication.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Division
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Cell Line
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Chromatids / physiology
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Chromatids / ultrastructure
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Chromosomes / physiology
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Chromosomes / ultrastructure
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DNA Replication*
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DNA-Activated Protein Kinase
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Humans
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In Situ Hybridization
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Mice
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Mitosis
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Mutation
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Nuclear Proteins
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / metabolism
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Telomere / metabolism*
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Telomeric Repeat Binding Protein 2
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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Nuclear Proteins
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Telomeric Repeat Binding Protein 2
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DNA-Activated Protein Kinase
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PRKDC protein, human
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Protein Serine-Threonine Kinases