DNA structure-dependent recruitment of telomeric proteins to single-stranded/double-stranded DNA junctions.
Telomeres protect chromosome ends by assembling unique protein-DNA complexes. TRF2 is a telomere binding protein that is involved in protecting the G-strand overhang, a 3', guanine-rich, overhang at the telomere terminus. TRF2 may protect the G-strand overhang by recognizing some organizational aspect of the telomeric single-stranded/double-stranded (ss/ds) DNA junction. This work demonstrates that TRF2, purified or in crude extracts, recognizes telomeric ss/ds DNA junctions containing wild type telomeric sequence in the ds region and a G-strand overhang with at least one telomeric repeat. Telomeric complexes containing TRF2 and pot1 assemble less efficiently when the G-strand overhang is in the form of an intramolecular G-quadruplex. However, recruitment of the DNA repair proteins, WRN, Mre11, and Ku86, is not inhibited by a G-quadruplex. This suggests that an intramolecular G-quadruplex has the potential to disrupt certain telomeric assemblies, but efficient recruitment of appropriate DNA repair proteins provides the means to overcome this obstacle.
Yanez
Giscard H
GH
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL, USA.
Khan
Sheik J
SJ
Locovei
Alexandra M
AM
Pedroso
Ilene M
IM
Fletcher
Terace M
TM
D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000737:chemistry; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D000089804:Shelterin Complex; D013329:Structure-Activity Relationship; D034501:Telomere-Binding Proteins / Q000737:chemistry*; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry*
D004277:DNA, Single-Stranded; D046911:Macromolecular Substances; C440849:POT1 protein, human; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA