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

The duplex telomere repeat (TTAGGG)(n) is an essential cis-acting element o f the mammalian telomere, and an exogenous telomere repeat can induce chrom osome breakage and de novo telomere formation at the site of a break (telom ere seeding). Telomere seeding requires the telomere repeat (TTAGGG)(n) mor e stringently than does an in vitro telomerase assay, suggesting that it re flects the activity of a critical trans-acting element of the functional te lomere, in addition to telomerase. Furthermore, telomere seeding is induced at a frequency fluctuating widely among human cell lines, suggesting varia tion in the activity of this hypothetical factor among cells. In this study , we investigated the cellular factor(s) required for telomere formation us ing the frequency of telomere seeding as an index and identified TRF1, one of the telomere repeat binding proteins, as an essential transacting factor . The exogenous telomere repeat induces telomere formation at a frequency d etermined by the availability of TRF1, even in telomerase-negative cells. O ur study shows clearly that TRF1 has a novel physiological significance dis tinct from its role as a regulator of telomere length in the endogenous chr omosome, The possible role of TRF1 in cell aging and immortalization is dis cussed.