Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2.
Human telomeres are composed of long arrays of TTAGGG repeats that form a nucleoprotein complex required for the protection and replication of chromosome ends. One component of human telomeres is the TTAGGG repeat binding factor 1 (TRF1), a ubiquitously expressed protein, related to the protooncogene Myb, that is present at telomeres throughout the cell cycle. Recent evidence has implicated TRF1 in the control of telomere length. TRF1 is proposed to be an inhibitor of telomerase, acting in cis to limit the elongation of individual chromosome ends. Here we report the cloning of TRF2, a distant homologue of TRF1 that carries a very similar Myb-related DNA-binding motif. Like TRF1, TRF2 was ubiquitously expressed, bound specifically to duplex TTAGGG repeats in vitro and localized to all human telomeres in metaphase chromosomes. TRF2 was shown to have an architecture similar to that of TRF1 in that it carries a C-terminal Myb motif and a large TRF1-related dimerization domain near its N terminus. However, the dimerization domains of TRF1 and TRF2 did not interact, suggesting that these proteins exist predominantly as homodimers. While having similar telomere binding activity and domain organization, TRF2 differed from TRF1 in that its N terminus was basic rather than acidic, and TRF2 was much more conserved than TRF1. The results indicate that the TTAGGG repeat arrays at the ends of human and mouse chromosomes bind to two related proteins. Because TRF1 and TRF2 showed significant differences, we suggest that these factors have distinct functions at telomeres.
Broccoli
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Rockefeller University, New York, New York 10021, USA.
Smogorzewska
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Chong
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de Lange
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009842:Oligopeptides; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D009842:Oligopeptides; D010455:Peptides; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D015534:Trans-Activators; C085706:FLAG peptide