Consequences of telomere shortening at an active VSG expression site in telomerase-deficient Trypanosoma brucei.
Trypanosoma brucei evades the host immune response by sequential expression of a large family of variant surface glycoproteins (VSG) from one of approximately 20 subtelomeric expression sites (ES). VSG transcription is monoallelic, and little is known about the regulation of antigenic switching. To explore whether telomere length could affect antigenic switching, we created a telomerase-deficient cell line, in which telomeres shortened at a rate of 3 to 6 bp at each cell division. Upon reaching a critical length, short silent ES telomeres were stabilized by a telomerase-independent mechanism. The active ES telomere progressively shortened and frequently broke. Upon reaching a critical length, the short active ES telomere stabilized, but the transcribed VSG was gradually lost from the population and replaced by a new VSG through duplicative gene conversion. We propose a model in which subtelomeric-break-induced replication-mediated repair at a short ES telomere leads to duplicative gene conversion and expression of a new VSG.
Dreesen
Oliver
O
Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6307, USA.
Cross
George A M
GA
D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics; D001483:Base Sequence; D016054:DNA, Protozoan / Q000235:genetics; D005785:Gene Conversion; D015870:Gene Expression; D017125:Genes, Protozoan; D008954:Models, Biological; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics*; D014346:Trypanosoma brucei brucei / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics* / Q000276:immunology*
D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D014643:Variant Surface Glycoproteins, Trypanosoma; D019098:Telomerase