TRF1 inhibits telomere C-strand DNA synthesis in vitro

Biochemistry
E J Smucker, J J Turchi

Abstract

Human TTAGGG repeat-binding factor 1 (TRF1) is involved in the regulation of telomere length in vivo, but the mechanism of regulation remains largely undefined. We have developed an in vitro system for assessing the effect of TRF1 on DNA synthesis using purified proteins and synthetic DNA substrates. Results reveal that TRF1, when bound to telomeric duplex DNA, inhibits DNA synthesis catalyzed by DNA polymerase alpha/primase (pol alpha). Inhibition required that TRF1 be bound to duplex telomeric DNA as no effect of TRF1 was observed on nontelomeric, random DNA substrates. Inhibition was shown to be dependent on TRF1 concentration and the length of the telomeric duplex region of the DNA substrate. When bound in cis to telomeric duplex DNA, TRF1 was also capable of inhibiting pol alpha-catalyzed DNA synthesis on nontelomeric DNA sequences from positions both upstream and downstream of the extending polymerase. Inhibition of DNA synthesis was shown to be specific for TRF1 but not necessarily for the DNA polymerase used in the extension reaction. In a series of control experiments, we assessed T7 DNA polymerase-catalyzed synthesis on a DNA template containing tandem gal4 operators. In these experiments, the addition of the purified...Continue Reading

References

May 2, 1997·The Journal of Biological Chemistry·P M RevealJ J Turchi
Apr 1, 1997·The EMBO Journal·A BianchiT de Lange
Apr 16, 1998·Current Biology : CB·C W Greider
Jun 16, 1999·The EMBO Journal·S MarcandE Gilson
Jan 15, 2000·The Journal of Biological Chemistry·O HammarstenG Chu

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Citations

Mar 10, 2004·Nucleic Acids Research·Rieko Ohki, Fuyuki Ishikawa
Sep 5, 2002·Microbiology and Molecular Biology Reviews : MMBR·Yu-Sheng CongJerry W Shay
Sep 4, 2007·Biochemical and Biophysical Research Communications·Hongtae Kim, Junjie Chen
Dec 15, 2005·Journal of Surgical Oncology·Jian HuXielai Zhou
Jul 2, 2004·Human Molecular Genetics·Kate Lillard-WetherellJoanna Groden
Jul 20, 2007·Cell Proliferation·M MatulićI Rubelj

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