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Switching human telomerase on and off with hPOT1 protein in vitro
Switching human telomerase on and off with hPOT1 protein in vitro.
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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.
Lei M, Zaug AJ, Podell ER, Cech TR
The Journal of biological chemistry
2005-05-27 00:00
280
21
20449-56
Alternative Splicing,Binding Sites,Crystallization,DNA,DNA Primers,DNA, Single-Stranded,Enzyme Inhibitors,Hemagglutinins,Humans,Models, Molecular,Molecular Structure,Oligonucleotides,Recombinant Proteins,Repetitive Sequences, Nucleic Acid,Structure-Activity Relationship,Substrate Specificity,Telomerase,Telomere,Telomere-Binding Proteins,DNA Primers,DNA, Single-Stranded,Enzyme Inhibitors,Hemagglutinins,Oligonucleotides,POT1 protein, human,Recombinant Proteins,Telomere-Binding Proteins,DNA,Telomerase
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA
J. Biol. Chem.
0021-9258
10.1074/jbc.M502212200
M502212200
279
True
15792951
