Telomerase consists of a reverse
transcriptase (TERT) and an RNA that contains a template for
telomere-repeat extension. Telomerase is required to prevent telomere
erosion and its activity or lack thereof is important for
tumorigenesis and ageing. Telomerase has been identified in numerous
organisms but it has not been studied in kinetoplastid protozoa.
Trypanosoma brucei, the causative agent of African sleeping sickness,
evades the host immune response by frequently changing its variant
surface glycoprotein (VSG). The single expressed VSG is transcribed
from one of 20 subtelomeric 'Expression Sites', but the role
telomeres might play in regulating VSG transcription and switching is
unknown. We identified and sequenced the T.brucei TERT gene. Deleting
TERT resulted in progressive telomere shortening of 3&endash;6 bp per
generation. In other organisms, the rate of telomere shortening is
proportional to the length of the terminal 3' single-strand overhang.
In T.brucei, G-overhangs were undetectable (<30 nt) by in-gel
hybridization. The rate of telomere shortening therefore, agrees with
the predicted shortening due to the end replication problem, and is
consistent with our observation that G-overhangs are short.
Trypanosomes whose telomere length can be manipulated provide a new
tool to investigate the role of telomeres in antigenic