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J Biol Chem, Vol. 275, Issue 19, 14509-14516, May 12, 2000

Heterogeneous Nuclear Ribonucleoprotein A1 and UP1 Protect Mammalian Telomeric Repeats and Modulate Telomere Replication in Vitro*

Frédéric DallaireDagger , Sophie DupuisDagger §, Stéphan Fiset, and Benoit Chabot

From the Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada

The heterogeneous nuclear ribonucleoprotein A1 protein and a shortened derivative (UP1) promote telomere elongation in mammalian cells. To gain insights into the function of A1/UP1 in telomere biogenesis, we have investigated the binding properties of recombinant A1/UP1 and derivatives to single-stranded DNA oligonucleotides. Our results indicate that UP1 prefers to bind to DNA carrying single-stranded telomeric extensions at the 3' terminus. The RNA recognition motif 1 is sufficient for strong and specific binding to oligomers carrying vertebrate telomeric repeats. We find that the binding of A1/UP1 protects telomeric sequences against degradation by endo- and exonucleases. Moreover, A1/UP1 binding prevents extension by telomerase and terminal deoxynucleotidyltransferase and inhibits rNTP-dependent DNA synthesis in vitro. These observations are consistent with the hypothesis that A1/UP1 is a telomere end-binding protein that plays a role in the maintenance of long 3' overhangs.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Recipient of a studentship from the Fonds pour la Formation de Chercheurs et l'Aide à la Recherche.

§ Present address: Dept. of Pediatrics, Division of Genetics, Washington University School of Medicine, One Children's Place, Box 8116, St. Louis, MO 63110.

Supported by a grant from the National Cancer Institute of Canada with funds from the Canadian Cancer Society. A Research Scholar from the Fonds de la Recherche en Santé du Québec. To whom correspondence should be addressed. Tel.: 819-564-5295; Fax: 819-564-5392; E-mail: b.chabot@courrier.usherb.ca.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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