Interactions of TRF2 with model telomeric ends

Khan, Sheik; Yanez, Giscard; Seldeen, Kenneth L.; Wang, Hongda; Lindsay, Stuart; Fletcher, Terace M.

doi:10.1016/j.bbrc.2007.08.122

Cited by 14 publications

(18 citation statements)

References 24 publications

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“…This suggests that the TRF2-driven, DNA self-association does not reside in this region. The linker region was previously found to stimulate oligomers on small model telomeric ends [50]. We found that the linker region contributed slightly to self-association as judged by a construct containing both the DBD and linker region (TRF2 DBD+L ), but the effect was not specific to DNA (data not shown).…”

Section: Resultsmentioning

confidence: 64%

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The Telomere Binding Protein TRF2 Induces Chromatin Compaction

Baker

Hayward

et al. 2011

PLoS ONE

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Mammalian telomeres are specialized chromatin structures that require the telomere binding protein, TRF2, for maintaining chromosome stability. In addition to its ability to modulate DNA repair activities, TRF2 also has direct effects on DNA structure and topology. Given that mammalian telomeric chromatin includes nucleosomes, we investigated the effect of this protein on chromatin structure. TRF2 bound to reconstituted telomeric nucleosomal fibers through both its basic N-terminus and its C-terminal DNA binding domain. Analytical agarose gel electrophoresis (AAGE) studies showed that TRF2 promoted the folding of nucleosomal arrays into more compact structures by neutralizing negative surface charge. A construct containing the N-terminal and TRFH domains together altered the charge and radius of nucleosomal arrays similarly to full-length TRF2 suggesting that TRF2-driven changes in global chromatin structure were largely due to these regions. However, the most compact chromatin structures were induced by the isolated basic N-terminal region, as judged by both AAGE and atomic force microscopy. Although the N-terminal region condensed nucleosomal array fibers, the TRFH domain, known to alter DNA topology, was required for stimulation of a strand invasion-like reaction with nucleosomal arrays. Optimal strand invasion also required the C-terminal DNA binding domain. Furthermore, the reaction was not stimulated on linear histone-free DNA. Our data suggest that nucleosomal chromatin has the ability to facilitate this activity of TRF2 which is thought to be involved in stabilizing looped telomere structures.

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Section: Resultsmentioning

confidence: 64%

“…Recombinant, His6-tagged TRF2 DBD+L and TRF2 BH (Figure S1) were expressed in E. coli BL21(D3) cells (Invitrogen) and purified according to [46], [50]. The basic N-terminal region of TRF2 (TRF2 B ), containing amino acids 2–31 and an N-terminal biotin followed by a lysine (Biotin-KAGGGGSSDGSGRAAGRRASRSSGRARRGRH) was synthesized by Invitrogen.…”

Section: Methodsmentioning

confidence: 99%

The Telomere Binding Protein TRF2 Induces Chromatin Compaction

Baker

Hayward

et al. 2011

PLoS ONE

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“…TRF2 plays an essential role in both telomere end protection (van Steensel et al, 1998; Karlseder et al, 1999; Karlseder et al, 2002; as reviewed by De Boeck et al, 2009) and T-loop formation (Griffith et al, 1999). Subsequent studies have shown that the TRF2 complex promotes T-loop formation via its interaction with telomere overhang, notably the 3′ guanine-rich termini (Griffith et al, 1999; Stansel et al, 2001; Khan et al, 2007; as reviewed by De Boeck et al, 2009). Thus, this system could potentially play an essential role in the protection of telomeres via the formation of higher-order structures, concealing overhang and preventing the degradation of telomeres at DNA damage checkpoints (De Boeck et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Regulation of the human catalytic subunit of telomerase (hTERT)

Daniel

Peek

Tollefsbol

2012

Gene

245

230

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Over the past decade, there has been much interest in the regulation of telomerase, the enzyme responsible for maintaining the integrity of chromosomal ends, and its crucial role in cellular immortalization, tumorigenesis, and the progression of cancer. Telomerase activity is characterized by the expression of the telomerase reverse transcriptase (TERT) gene, suggesting that TERT serves as the major limiting agent for telomerase activity. Recent discoveries have led to characterization of various interactants that aid in the regulation of human TERT (hTERT), including numerous transcription factors; further supporting the pivotal role that transcription plays in both the expression and repression of telomerase. Several studies have suggested that epigenetic modulation of the hTERT core promoter region may provide an additional level of regulation. Although these studies have provided essential information on the regulation of hTERT, there has been ambiguity of the role of methylation within the core promoter region and the subsequent binding of various activating and repressive agents. As a result, we found it necessary to consolidate and summarize these recent developments and elucidate these discrepancies. In this review, we focus on the co-regulation of hTERT via transcriptional regulation, the presence or absence of various activators and repressors, as well as the epigenetic pathways of DNA methylation and histone modifications.

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“…The ability of Esherichia coli single-strand-binding protein to bind to the junction of the loop suggests the presence of some form of single-stranded or other non-duplex DNA structures (10). TRF2 was able to stimulate the formation of t-loops in vitro , partly through its ability to oligomerize through its TRF homology (TRFH) domain (11) and possibly via a structurally uncharacterized linker region (12). In addition to interacting with double-stranded telomeric DNA, TRF2 interacts with other DNA motifs such as three-way, four-way (13) and single-strand/double-strand DNA junctions (12).…”

Section: Introductionmentioning

confidence: 99%

“…TRF2 was able to stimulate the formation of t-loops in vitro , partly through its ability to oligomerize through its TRF homology (TRFH) domain (11) and possibly via a structurally uncharacterized linker region (12). In addition to interacting with double-stranded telomeric DNA, TRF2 interacts with other DNA motifs such as three-way, four-way (13) and single-strand/double-strand DNA junctions (12). Binding to these structures is likely to involve a glycine/arginine-rich region in the N-terminus (13).…”

Section: Introductionmentioning

confidence: 99%

The effect of the TRF2 N-terminal and TRFH regions on telomeric G-quadruplex structures

Pedroso

Hayward

Fletcher

2009

Nucleic Acids Research

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The sequence of human telomeric DNA consists of tandem repeats of 5′-d(TTAGGG)-3′. This guanine-rich DNA can form G-quadruplex secondary structures which may affect telomere maintenance. A current model for telomere protection by the telomere-binding protein, TRF2, involves the formation of a t-loop which is stabilized by a strand invasion-like reaction. This type of reaction may be affected by G-quadruplex structures. We analyzed the influence of the arginine-rich, TRF2 N-terminus (TRF2B), as well as this region plus the TRFH domain of TRF2 (TRF2BH), on the structure of G-quadruplexes. Circular dichroism results suggest that oligonucleotides with 4, 7 and 8 5′-d(TTAGGG)-3′ repeats form hybrid structures, a mix of parallel/antiparallel strand orientation, in K+. TRF2B stimulated the formation of parallel-stranded structures and, in some cases, intermolecular structures. TRF2BH also stimulated intermolecular but not parallel-stranded structures. Only full-length TRF2 and TRF2BH stimulated uptake of a telomeric single-stranded oligonucleotide into a plasmid containing telomeric DNA in the presence of K+. The results in this study suggest that G-quadruplex formation inhibits oligonucleotide uptake into the plasmid, but the inhibition can be overcome by TRF2. This study is the first analysis of the effects of TRF2 domains on G-quadruplex structures and has implications for the role of G-quadruplexes and TRF2 in the formation of t-loops.

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Interactions of TRF2 with model telomeric ends

Cited by 14 publications

References 24 publications

The Telomere Binding Protein TRF2 Induces Chromatin Compaction

The Telomere Binding Protein TRF2 Induces Chromatin Compaction

Regulation of the human catalytic subunit of telomerase (hTERT)

The effect of the TRF2 N-terminal and TRFH regions on telomeric G-quadruplex structures

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