Control of Telomere Length by a Trimming Mechanism That Involves Generation of T-circles

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2009 Feb 14

PMID 19214183

Citations 117

Authors

Hilda A Pickett

Anthony J Cesare

Rebecca L Johnston

Axel A Neumann

Roger R Reddel

Affiliations

Soon will be listed here.

Abstract

Telomere lengths are maintained in many cancer cells by the ribonucleoprotein enzyme telomerase but can be further elongated by increasing telomerase activity through the overexpression of telomerase components. We report here that increased telomerase activity results in increased telomere length that eventually reaches a plateau, accompanied by the generation of telomere length heterogeneity and the accumulation of extrachromosomal telomeric repeat DNA, principally in the form of telomeric circles (t-circles). Telomeric DNA was observed in promyelocytic leukemia bodies, but no intertelomeric copying or telomere exchange events were identified, and there was no increase in telomere dysfunction-induced foci. These data indicate that human cells possess a mechanism to negatively regulate telomere length by trimming telomeric DNA from the chromosome ends, most likely by t-loop resolution to form t-circles. Additionally, these results indicate that some phenotypic characteristics attributed to alternative lengthening of telomeres (ALT) result from increased mean telomere length, rather than from the ALT mechanism itself.

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