Abstract
POT1 (protection of telomeres 1) protein binds the G-rich single-stranded telomeric DNA at the ends of chromosomes. In human cells hPOT1 is involved in telomere length regulation, but the mechanism of this regulation remains unknown. Examination of the high-resolution crystal structure of the hPOT1-TTAGGGTTAG complex suggested that it would not be extended by telomerase, a hypothesis that we confirm by in vitro assays with recombinant telomerase. On the other hand, when hPOT1 is bound at a position one telomeric repeat before the 3'-end, leaving an 8-nucleotide 3'-tail, the complex is extended with improved activity and processivity. Thus, depending on its location relative to the DNA 3'-end, hPOT1 can either inhibit telomerase action or form a preferred substrate for telomerase. We propose that another factor catalyzes the interconversion of these states in vivo.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alternative Splicing
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Binding Sites
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Crystallization
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DNA / metabolism
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DNA Primers
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DNA, Single-Stranded / chemistry
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DNA, Single-Stranded / metabolism
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Enzyme Inhibitors
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Hemagglutinins
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Humans
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Models, Molecular
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Molecular Structure
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Oligonucleotides / chemistry
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Oligonucleotides / metabolism
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Recombinant Proteins / metabolism
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Repetitive Sequences, Nucleic Acid
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Shelterin Complex
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Structure-Activity Relationship
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Substrate Specificity
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Telomerase / antagonists & inhibitors
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Telomerase / metabolism*
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Telomere / chemistry
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Telomere / genetics
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Telomere-Binding Proteins / chemistry
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Telomere-Binding Proteins / genetics
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Telomere-Binding Proteins / metabolism*
Substances
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DNA Primers
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DNA, Single-Stranded
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Enzyme Inhibitors
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Hemagglutinins
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Oligonucleotides
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POT1 protein, human
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Recombinant Proteins
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Shelterin Complex
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Telomere-Binding Proteins
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DNA
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Telomerase