Regulation of Catalytic Activity and Processivity of Human Telomerase

The ends of eukaryotic chromosomes are specialized sequences, called telomeres comprising tandem repeats of simple DNA sequences. Those sequences are essential for preventing aberrant recombination and protecting genomic DNA against exonucleolytic DNA degradation. Telomeres are maintained at a stabl...

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Bibliographic Details
Published in:Biochemistry (Easton) 1999-03, Vol.38 (13), p.4037-4044
Main Authors: Sun, Daekyu, Lopez-Guajardo, Christine C, Quada, James, Hurley, Laurence H, Von Hoff, Daniel D
Format: Article
Language:English
Subjects:
Catalysis
Deoxyguanine Nucleotides - chemistry
Deoxyguanine Nucleotides - metabolism
DNA Primers - chemistry
DNA Primers - metabolism
Enzyme Activation - genetics
HeLa Cells
Humans
Models, Biological
Models, Chemical
Potassium - chemistry
Potassium - metabolism
Protein Processing, Post-Translational - genetics
Telomerase - chemistry
Telomerase - genetics
Telomerase - metabolism
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Summary:The ends of eukaryotic chromosomes are specialized sequences, called telomeres comprising tandem repeats of simple DNA sequences. Those sequences are essential for preventing aberrant recombination and protecting genomic DNA against exonucleolytic DNA degradation. Telomeres are maintained at a stable length by telomerase, an RNA-dependent DNA polymerase. Recently, human telomerase has been recognized as a unique diagnostic marker for human tumors and is potentially a highly selective target for antitumor drugs. In this study, we have examined the major factors affecting the catalytic activity and processivity of human telomerase. Specifically, both the catalytic activity and processivity of human telomerase were modulated by temperature, substrate (dNTP and primer) concentration, and the concentration of K+. The catalytic activity of telomerase increased as temperature (up to 37 °C), concentrations of dGTP, primer, and K+ were increased. However, the processivity of human telomerase decreased as temperature, primer concentration, and K+ were increased. Our results support the current model for human telomerase reaction and strengthen the hypothesis that a G-quadruplex structure of telomere DNA plays an important role in the regulation of the telomerase reaction.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi982249n