RRC ID 39884
Author Okabe J, Eguchi A, Masago A, Hayakawa T, Nakanishi M.
Title TRF1 is a critical trans-acting factor required for de novo telomere formation in human cells.
Journal Hum. Mol. Genet.
Abstract 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.
Volume 9(18)
Pages 2639-50
Published 2000-11-1
DOI 10.1093/hmg/9.18.2639
PMID 11063723
MeSH Base Sequence Blotting, Western Cell Line Cell Survival Cellular Senescence DNA-Binding Proteins / metabolism DNA-Binding Proteins / physiology* Gene Deletion Humans Repetitive Sequences, Nucleic Acid / genetics Telomerase / genetics Telomerase / metabolism Telomere / genetics* Telomere / metabolism Telomeric Repeat Binding Protein 1 Trans-Activators / metabolism Trans-Activators / physiology*
IF 4.544
Times Cited 24
Human and Animal Cells