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This paper describes the NMR solution structure of the DNA-binding domain of the human TRF1 telomere-binding protein bound to two repeats of human telomeric DNA. One helix of TRF1 is involved in sequence-specific binding to the TTAGGG repeat, using both major and minor groove hydrogen bonding.
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A detailed NMR analysis, showing that even a minor sequence difference can result in major structural changes to the folding of the Oxytricha quadruplex.
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The crystal structures of quadruplexes formed from 12- and 22-mer human telomere sequences are reported, both containing bound potassium ions. The 22-mer sequence is identical to that used in the earlier NMR study [24]. Both structures show the same features of all-parallel strands and external d(TTA) loops, resulting in flattened, propeller-shaped structures that can readily stack one upon the other. The loops show marked conservation of structure; in every one, the adenine base is found to be intercalated between the two thymines.
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An elegant demonstration that the quadruplex-binding porphyrin ligand can induce a quadruplex structure to be formed within a duplex sequence and that this can inhibit transcription of the c-myc gene. The study used site-directed mutagenesis to show that a single base change in the putative quadruplex-forming sequence abolished both quadruplex formation and transcription inhibition.
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Siddiqui-Jain A., Grand C.L., Bearss D.J., Hurley L.H. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc. Natl. Acad Sci. USA. 99:2002;11593-11598 An elegant demonstration that the quadruplex-binding porphyrin ligand can induce a quadruplex structure to be formed within a duplex sequence and that this can inhibit transcription of the c-myc gene. The study used site-directed mutagenesis to show that a single base change in the putative quadruplex-forming sequence abolished both quadruplex formation and transcription inhibition.
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4). The antibody probes selected have affinities in the low nanomolar range and showed specific reaction with the macronuclei of this ciliate, providing evidence of the existence of quadruplexes in vivo; these appear only during nonreplicative stages.
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Read M.A., Harrison R.J., Romagnoli B., Tanious F.A., Gowan S.M., Reszka A.P., Wilson W.D., Kelland L.R., Neidle S. Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors. Proc. Natl. Acad Sci. USA. 98:2001;4844-4849 Rational structure approaches were used to design ligands with enhanced selectivity for the human 22-mer G-quadruplex, and increased selectivity and potency for telomerase inhibition.
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This paper reports the crystal structure of an acridine derivative specifically bound within one of the d(TTTT) loops of the Oxytricha G-quadruplex.
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Cooperative binding of single-stranded telomeric DNA by the Pot1 protein of Schizosaccharomyces pombe
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A detailed study of the binding of Pot1 to single-stranded telomeric DNA, showing that it binds sequence specifically and cooperatively, suggesting that several Pot1 molecules may be bound to the overhang in vivo.
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Lei M., Baumann P., Cech T.R. Cooperative binding of single-stranded telomeric DNA by the Pot1 protein of Schizosaccharomyces pombe. Biochemistry. 41:2002;14560-14568 A detailed study of the binding of Pot1 to single-stranded telomeric DNA, showing that it binds sequence specifically and cooperatively, suggesting that several Pot1 molecules may be bound to the overhang in vivo.
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Opresko P.L., von Kobbe C., Laine J.P., Harrigan J., Hickson I.D., Bohr V.A. Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J. Biol. Chem. 277:2002;41110-41119.
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Inhibition of the Bloom's and Werner's syndrome helicases by G-quadruplex interacting ligands
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Li J.L., Harrison R.J., Reszka A.P., Brosh R.M. Jr., Bohr V.A., Neidle S., Hickson I.D. Inhibition of the Bloom's and Werner's syndrome helicases by G-quadruplex interacting ligands. Biochemistry. 40:2001;15194-15202.
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Li, J.L.1
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Neidle, S.6
Hickson, I.D.7
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Down-regulation of TRF1, TRF2 and TIN2 genes is important to maintain telomeric DNA for gastric cancers
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Yamada M., Tsuji N., Nakamur M., Moriai R., Kobayashi D., Yagihashi A., Watanabe N. Down-regulation of TRF1, TRF2 and TIN2 genes is important to maintain telomeric DNA for gastric cancers. Anticancer Res. 22:2002;3303-3307.
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Yamada, M.1
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Yagihashi, A.6
Watanabe, N.7
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50
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Ku is required for telomeric C-rich strand maintenance but not for end-to-end chromosome fusions in Arabidopsis
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Riha K., Shippen D.E. Ku is required for telomeric C-rich strand maintenance but not for end-to-end chromosome fusions in Arabidopsis. Proc. Natl. Acad Sci. USA. 100:2003;611-615.
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Riha, K.1
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Different telomere damage signaling pathways in human and mouse cells
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This paper highlights some of the major differences in telomere biology between mice and humans.
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Smogorzewska A., de Lange T. Different telomere damage signaling pathways in human and mouse cells. EMBO J. 21:2002;4338-4348 This paper highlights some of the major differences in telomere biology between mice and humans.
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Association of p16(INK4a) and pRb inactivation with immortalization of human cells
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Tsutsui T., Kumakura S., Yamamoto A., Kanai H., Tamura Y., Kato T., Anpo M., Tahara H., Barrett J.C. Association of p16(INK4a) and pRb inactivation with immortalization of human cells. Carcinogenesis. 12:2002;2111-2117.
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Carcinogenesis
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Tsutsui, T.1
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Yamamoto, A.3
Kanai, H.4
Tamura, Y.5
Kato, T.6
Anpo, M.7
Tahara, H.8
Barrett, J.C.9
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