The Human Pif1 Helicase, a Potential Escherichia Coli RecD Homologue, Inhibits Telomerase Activity

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2006 Mar 9

PMID 16522649

Citations 52

Authors

Deng-Hong Zhang

Bo Zhou

Yu Huang

Lu-Xia Xu

Jin-Qiu Zhou

Affiliations

Soon will be listed here.

Abstract

Telomeres, the protein-DNA complexes at the ends of eukaryotic chromosomes, are essential for chromosome stability, and their maintenance is achieved by the specialized reverse transcriptase activity of telomerase or the homologous recombination pathway in most eukaryotes. Here, we identified a human helicase, hPif1 that inhibits telomerase activity. The primary sequence and biochemical analysis suggest that hPif1 is a potential homologue of Escherichia coli RecD, an ATP-dependent 5' to 3' DNA helicase. Ectopic expression of wild-type, but not the ATPase/helicase-deficient hPif1, causes telomere shortening in HT1080 cells. hPif1 reduces telomerase processivity and unwinds DNA/RNA duplex in vitro. hPif1 preferentially binds telomeric DNA in vitro and in vivo. We propose that the mechanism of hPif1's inhibition on telomerase involves unwinding of the DNA/RNA duplex formed by telomerase RNA and telomeric DNA, and RecD homologues in eukaryotes may have evolved gaining additional functions.

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