The basic domain of TRF2 directs binding to DNA junctions irrespective of the presence of TTAGGG repeats.
The replication of long tracts of telomeric repeats may require specific factors to avoid fork regression (Fouché, N., Ozgür, 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(DeltaB)) 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.
Fouché
Nicole
N
Lineberger Comprehensive Cancer Center and Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Cesare
Anthony J
AJ
Willcox
Smaranda
S
Ozgür
Sezgin
S
Compton
Sarah A
SA
Griffith
Jack D
JD
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015342:DNA Probes / Q000235:genetics; D045566:DNA, Cruciform / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D035182:TATA Box Binding Protein-Like Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2
D015342:DNA Probes; D045566:DNA, Cruciform; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D035182:TATA Box Binding Protein-Like Proteins; C504753:TERF2 protein, human; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA