title: Telomerase-independent stabilization of short telomeres in Trypanosoma brucei.
abstract: In cancer cells and germ cells, shortening of chromosome ends is prevented by telomerase. Telomerase-deficient cells have a replicative life span, after which they enter senescence. Senescent cells can give rise to survivors that maintain chromosome ends through recombination-based amplification of telomeric or subtelomeric repeats. We found that in Trypanosoma brucei, critically short telomeres are stable in the absence of telomerase. Telomere stabilization ensured genomic integrity and could have implications for telomere maintenance in human telomerase-deficient cells. Cloning and sequencing revealed 7 to 27 TTAGGG repeats on stabilized telomeres and no changes in the subtelomeric region. Clones with short telomeres were used to study telomere elongation dynamics, which differed dramatically at transcriptionally active and silent telomeres, after restoration of telomerase. We propose that transcription makes the termini of short telomeres accessible for rapid elongation by telomerase and that telomere elongation in T. brucei is not regulated by a protein-counting mechanism. Many minichromosomes were lost after long-term culture in the absence of telomerase, which may reflect their different mitotic segregation properties.
authors.affiliation: Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dreesen
authors.forename: George A M
authors.initials: GA
authors.lastname: Cross
mesh_terms: D000818:Animals; D002875:Chromosomes / Q000378:metabolism; D016054:DNA, Protozoan / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017384:Sequence Deletion; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics*
chemical_list: D016054:DNA, Protozoan; D019098:Telomerase