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J. Biol. Chem., Vol. 282, Issue 26, 18786-18792, June 29, 2007

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Protection of DNA Ends by Telomeric 3' G-Tail Sequences^*

From the Department of Pharmacology, University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

The extreme ends of eukaryotic chromosomes contain 3' extensions in the form of single-stranded G-rich repeats, referred to as telomeric 3' G-tails or overhangs. Increasing evidence has suggested that telomeric 3' G-tails can adopt a G-quadruplex conformation both in vitro and in vivo. However, the role of G-quadruplexes on the structure and function of telomeric 3' G-tails remains unclear. In the current study, we showed that the human telomeric 3' G-tail sequence protected the duplex DNA ends in cis from being recognized as double strand breaks. This protection is dependent on the G-quadruplex conformation of the 3' G-tail sequence. These results suggest that the ability of telomeric 3' G-tails to adopt the endprotecting G-quadruplex conformation may be one of the reasons for the existence of the evolutionarily conserved G-stretch motifs in telomeric DNA sequences.

Received for publication, March 13, 2007 , and in revised form, April 23, 2007.

^* This work was supported by National Institutes of Health Grants CA102463 and CA39662 (to L. F. L.), New Jersey Commission for Cancer Research Grant 04-2408-CCR-E0 (to H. Q.), and U. S. Department of Defense Grant BC045756 (to H. Q.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854. Tel.: 732-235-4592; Fax: 732-235-4073; E-mail: lliu{at}umdnj.edu.

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