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Originally published In Press as doi:10.1074/jbc.M608778200 on October 18, 2006

J. Biol. Chem., Vol. 281, Issue 49, 37486-37495, December 8, 2006
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The Basic Domain of TRF2 Directs Binding to DNA Junctions Irrespective of the Presence of TTAGGG Repeats*

Nicole Fouché{ddagger}, Anthony J. Cesare§, Smaranda Willcox{ddagger}, Sezgin Özgür{ddagger}, Sarah A. Compton{ddagger}, and Jack D. Griffith{ddagger}1

From the {ddagger}Lineberger Comprehensive Cancer Center and Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 and §Cancer Research Unit, Children's Medical Research Institute, Westmead, New South Wales 2145, Australia

The replication of long tracts of telomeric repeats may require specific factors to avoid fork regression (Fouché, N., Özgür, S., Roy, D., and Griffith, J. (2006) Nucleic Acids Res., in press). Here we show that TRF2 binds to model replication forks and four-way junctions in vitro in a structure-specific but sequence-independent manner. A synthetic peptide encompassing the TRF2 basic domain also binds to DNA four-way junctions, whereas the TRF2 truncation mutant (TRF2{Delta}B) and a mutant basic domain peptide do not. In the absence of the basic domain, the ability of TRF2 to localize to model telomere ends and facilitate t-loop formation in vitro is diminished. We propose that TRF2 plays a key role during telomere replication in binding chickenfoot intermediates of telomere replication fork regression. Junction-specific binding would also allow TRF2 to stabilize a strand invasion structure that is thought to exist at the strand invasion site of the t-loop.


Received for publication, September 11, 2006 , and in revised form, October 18, 2006.

* This work was supported in part by the Ellison Medical Foundation and National Institutes of Health Grants GM31819 and ES013773 (to J. D. G.). 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. Tel.: 919-966-2151; Fax: 919-966-3015; E-mail: jdg{at}med.unc.edu.


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