The Human Telomeric Protein TRF1 Specifically Recognizes Nucleosomal Binding Sites and Alters Nucleosome Structure

Galati, Alessandra; Rossetti, Luigi; Pisano, Sabrina; Chapman, Lynda; Rhodes, Daniela; Savino, M.; Cacchione, Stefano

doi:10.1016/j.jmb.2006.04.071

Cited by 32 publications

(39 citation statements)

References 44 publications

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“…For instance, the shelterin component TRF1, which can bind telomeric DNA within a nucleosomal context, has been shown to modulate nucleosome structure (13). It is also interesting to note that nucleosomes assembled on telomeric sequences under physiologic conditions appear intrinsically more mobile than those assembled on average DNA (33) and that the telomeric core particles appear highly sensitive to nucleases.…”

Section: Discussionmentioning

confidence: 99%

No Overt Nucleosome Eviction at Deprotected Telomeres

Lange

2008

Molecular and Cellular Biology

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Dysfunctional telomeres elicit the canonical DNA damage response, which includes the activation of the ATM or ATR kinase signaling pathways and end processing by nonhomologous end joining (NHEJ) or homologous recombination (HR). The cellular response to DNA double-strand breaks has been proposed to involve chromatin remodeling and nucleosome eviction, but whether dysfunctional telomeres undergo chromatin reorganization is not known. Here, we report on the nucleosomal organization of telomeres that have become deprotected through the deletion of the shelterin components TRF2 or POT1. We found no evidence of changes in the nucleosomal organization of the telomeric chromatin or nucleosome eviction near the telomere terminus. An unaltered chromatin structure was observed at telomeres lacking TRF2, which activate the ATM kinase and are a substrate for NHEJ. Similarly, telomeres lacking POT1a and POT1b, which activate the ATR kinase, showed no overt nucleosome eviction. Finally, telomeres lacking TRF2 and Ku70, which are processed by HR, appeared to maintain their original nucleosomal organization. We conclude that ATM signaling, ATR signaling, NHEJ, and HR at deprotected telomeres can take place in the absence of overt nucleosome eviction.Through their unique structure and composition, specialized nucleoprotein complexes known as telomeres protect the ends of linear chromosomes. Vertebrate telomeres can form socalled t-loops through strand invasion of their long 3Ј overhang into the double-stranded region of telomeric TTAGGG repeats (17, 32). Beyond this ultrastructure, the packaging of telomeric DNA in nucleosomal chromatin lends an additional layer of complexity to vertebrate telomeres. Whereas Saccharomyces cerevisiae and Tetrahymena spp. have short, nonnucleosomal telomeres (7,16,43), the results of electron microscopy and micrococcal nuclease (MNase) digestion studies have demonstrated the presence of nucleosomes at telomeres in a number of vertebrates, including chickens, rodents, and humans (26,28,32,38). Telomeric chromatin resembles bulk chromatin in its composition, consisting of the canonical core histone components, but the nucleosomal repeat length is short, and the nucleosomal core particle shows hypersensitivity to MNase (26,28,38). The results of in vitro studies have shown that nucleosomes assembled on TTAGGG repeats exhibit higher mobility than on other sequences (33). In addition, telomeric chromatin is enriched for heterochromatic marks, such as trimethylation of H3K9 and H4K20, and the results of studies in mice have shown that the loss of such marks correlates with abnormally elongated telomeres (3, 14, 15). Short human telomeres show evidence of an unusual chromatin structure, as deduced from the more diffuse nature of the MNase digestion patterns (38), but the molecular basis of this change is not known.Shelterin, a six-protein complex unique to chromosome ends, binds TTAGGG repeats within their nucleosomal context and protects telomeres from being recognized as DNA double-strand breaks (DSBs)...

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Section: Discussionmentioning

confidence: 99%

No Overt Nucleosome Eviction at Deprotected Telomeres

Lange

2008

Molecular and Cellular Biology

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“…In addition to shelterin, telomeric DNA is associated with nucleosomes (Makarov et al 1993;Tommerup et al 1994;Lejnine et al 1995;Nikitina and Woodcock 2004;Wu and de Lange 2008). The details of how shelterin binds to nucleosomal chromatin are beginning to be addressed (Galati et al 2006;Baker et al 2009). It should also be noted that shelterin components, in particular TRF1 and TRF2, can be modified in numerous ways (parsylation, ubiquitylation, sumoylation, phosphorylation, Arg methylation, and prolyl isomerization) and the functional consequences of these modifications are being explored (Smith et al 1998;Lee et al 2006Lee et al , 2009Potts and Yu 2007;Kim et al 2008;Atanassov et al 2009;Chen et al 2009;Her and Chung 2009;Zeng et al 2010).…”

Section: Shelterin: a Sextet Of Protective Proteinsmentioning

confidence: 99%

How Shelterin Solves the Telomere End-Protection Problem

Lange

2010

Cold Spring Harbor Symposia on Quantitative Biology

150

121

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“…An analysis of the association of several proteins to telomeres using a ChIP assay, showed that TRF1 binds to 20-30 % of telomeric tracts, whereas TRF2 binds to about 15 % [104]. Since most of telomeric DNA is packed in nucleosomes, a possible hypothesis is that TRF proteins, after saturating the short DNA linkers between nucleosomes, could interact with nucleosomal binding sites [106]. Indeed, yeast Rap1 protein and human TRF1 are able to specifically recognize their binding sites located on nucleosome surface, forming a specific ternary complex [105,106].…”

Section: Peculiar Features Of Telomeric Nucleosomesmentioning

confidence: 99%

“…Since most of telomeric DNA is packed in nucleosomes, a possible hypothesis is that TRF proteins, after saturating the short DNA linkers between nucleosomes, could interact with nucleosomal binding sites [106]. Indeed, yeast Rap1 protein and human TRF1 are able to specifically recognize their binding sites located on nucleosome surface, forming a specific ternary complex [105,106]. yRap1 binds to the nucleosome with a threefold lower affinity with respect to naked DNA.…”

Section: Peculiar Features Of Telomeric Nucleosomesmentioning

confidence: 99%

Telomeric nucleosomes: Forgotten players at chromosome ends

Pisano

Galati

Cacchione

2008

Cell. Mol. Life Sci.

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Telomeres are the special nucleoprotein structures that protect chromosome ends from both recombination and degradation. In most organisms, telomeric DNA consists of short sequences repeated in tandem ending in single-stranded G-rich overhangs. In higher eukaryotes, about 80% of telomeric DNA is organized in tightly packed nucleosomes separated by 10-20 bp of linker DNA. Several specific proteins contribute to telomeric structure. At the moment, a satisfactory description of telomere organization is still lacking. Whereas the role played by telomeric proteins in telomere function and regulation has been widely investigated, little is known about the contribution of nucleosomes to the protection of chromosome ends. In this review we present an overview on the chromatin organization in lower and higher eukaryotes, and discuss the recent results on the peculiar features of telomeric nucleosomes and on the epigenetic status of mammalian telomeres.

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The Human Telomeric Protein TRF1 Specifically Recognizes Nucleosomal Binding Sites and Alters Nucleosome Structure

Cited by 32 publications

References 44 publications

No Overt Nucleosome Eviction at Deprotected Telomeres

No Overt Nucleosome Eviction at Deprotected Telomeres

How Shelterin Solves the Telomere End-Protection Problem

Telomeric nucleosomes: Forgotten players at chromosome ends

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