A Human Telomeric Protein

Chong, Laura; Steensel, Bas van; Broccoli, Dominique; Erdjument‐Bromage, Hediye; Hanish, John; Tempst, Paul; Lange, Titia de

doi:10.1126/science.270.5242.1663

Cited by 621 publications

(453 citation statements)

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“…This corroborates the finding in Fig. 5A, and proves that telomeres in the cells expressing TRF1 get shorter with time, presumably due to binding of TRF1, which is highly specific for TTAGGG repeat units [6,7,39,45,46] and co-localized with trypanosome telomeres, within the limits of optical resolution ( Fig. 2A).…”

Section: Trypanosomes Expressing Trf1 Exhibit Telomere Shorteningsupporting

confidence: 90%

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Telomere shortening and cell cycle arrest in Trypanosoma brucei expressing human telomeric repeat factor TRF1

Muñoz‐Jordán

Cross

2001

Molecular and Biochemical Parasitology

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Trypanosoma brucei has telomeres composed of 15 kb tracts of TTAGGG repeats that end in 3% overhangs and form t-loops. This structure is also present in mammalian cells and is thought to reflect the presence of telomere-binding proteins. The human TTAGGG repeat-binding factor TRF1 binds to telomeres and regulates their length. We attempted to interfere with the normal function of trypanosome telomeres by expressing human TRF1 in T. brucei. TRF1 localized to telomeres in cultured procyclic (midgut-stage) trypanosomes with great fidelity, but not in bloodstream-stage trypanosomes. Procyclic trypanosomes expressing high levels of TRF1 for extended periods of time exhibited shortening and increased size heterogeneity of their telomeres and the cell cycle was arrested in G1-S. These effects were not detected in cells expressing a TRF1 mutant incapable of binding to TTAGGG repeats. We argue that TRF1 displaces putative endogenous trypanosome telomere-binding proteins, not yet identified, and affects telomeres in ways that reflect its role as a negative regulator of telomere length in human cells.

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Section: Trypanosomes Expressing Trf1 Exhibit Telomere Shorteningsupporting

confidence: 90%

“…A protocol was adapted for trypanosomes from previously published procedures [39]. BF or PF diluted to 10 6 trypanosomes ml − 1 in TDB or PBS, respectively were attached to glass coverslips by centrifugation at 3000× g for 5 min at 4°C.…”

Section: In Situ Hybridization and Immunofluorescencementioning

confidence: 99%

Telomere shortening and cell cycle arrest in Trypanosoma brucei expressing human telomeric repeat factor TRF1

Muñoz‐Jordán

Cross

2001

Molecular and Biochemical Parasitology

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“…Mammalian telomeres consist of several kilobases of tandem TTAGGG repeats bound by speci®c proteins (Chong et al, 1995). They play numerous roles in the maintenance of chromosomal integrity and cell viability (Blackburn, 1991).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

et al. 2000

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“…This hypothesis was investigated in a population-based case -control study of breast cancer study in Poland, in which we genotyped 24 common SNPs that captured most of the common genetic variation in five genes important in telomere biology. The studied genes included telomerase (TERT (protein name), TERT (HUGO gene name), 5p15.33) (Collins and Mitchell, 2002), telomerase-associated protein (TP1, TEP1, 14q11.2) (Poderycki et al, 2005), telomeric repeat-binding factor 1 (TRF1, TERF1, 8q13) (Smogorzewska et al, 2000), telomeric repeat-binding factor 2 (TRF2, TERF2, 16q22.1) (Chong et al, 1995;Broccoli et al, 1997) and protection of telomeres 1 (POT1, POT1, 7q31.33) (Baumann and Cech, 2001). …”

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Genetic variation in five genes important in telomere biology and risk for breast cancer

et al. 2007

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Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (À1381C4T, À244C4T, and Ex2-659G4A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53 -1.00, 0.46 -0.95 and 0.39 -0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies.

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A Human Telomeric Protein

Cited by 621 publications

References 44 publications

Telomere shortening and cell cycle arrest in Trypanosoma brucei expressing human telomeric repeat factor TRF1

Telomere shortening and cell cycle arrest in Trypanosoma brucei expressing human telomeric repeat factor TRF1

Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

Genetic variation in five genes important in telomere biology and risk for breast cancer

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