Journal Article

TRF1 is a critical <i>trans</i>-acting factor required for <i> de novo</i> telomere formation in human cells

Jun Okabe, Akiko Eguchi, Akinori Masago, Takao Hayakawa and Mahito Nakanishi

in Human Molecular Genetics

Volume 9, issue 18, pages 2639-2650
Published in print November 2000 | ISSN: 0964-6906
Published online November 2000 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/9.18.2639
TRF1 is a critical trans-acting factor required for  de novo telomere formation in human cells

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The duplex telomere repeat (TTAGGG)n is an essential cis-acting element of the mammalian telomere, and an exogenous telomere repeat can induce chromosome breakage and de novo telomere formation at the site of a break (telomere seeding). Telomere seeding requires the telomere repeat (TTAGGG)n more stringently than does an in vitro telomerase assay, suggesting that it reflects the activity of a critical trans-acting element of the functional telomere, in addition to telomerase. Furthermore, telomere seeding is induced at a frequency fluctuating widely among human cell lines, suggesting variation in the activity of this hypothetical factor among cells. In this study, we investigated the cellular factor(s) required for telomere formation using the frequency of telomere seeding as an index and identified TRF1, one of the telomere repeat binding proteins, as an essential trans-acting factor. The exogenous telomere repeat induces telomere formation at a frequency determined by the availability of TRF1, even in telomerase-negative cells. Our study shows clearly that TRF1 has a novel physiological significance distinct from its role as a regulator of telomere length in the endogenous chromosome. The possible role of TRF1 in cell aging and immortalization is discussed.

Journal Article.  9317 words.  Illustrated.

Subjects: Genetics and Genomics

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