Regulation of catalytic activity and processivity of human telomerase

Daekyu Sun, Christine C. Lopez-Guajardo, James Quada, Laurence H. Hurley, Daniel D. Von Hoff

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4037-4044
Number of pages8
JournalBiochemistry
Volume38
Issue number13
DOIs
StatePublished - Mar 30 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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