Biochemical properties of Trypanosoma cruzi telomerase.
Trypanosomatid parasite infections have a devastating impact on human health. Little is known about the requirements for parasite growth during any stage of their complex, multi-host life cycle. In most eukaryotic organisms, sustained cell proliferation requires telomerase-dependent telomere length maintenance. Here we investigate the regulation and biochemical features of telomerase from Trypanosoma cruzi, the causative agent of Chagas disease. We found that T.cruzi telomerase is active in extracts from multiple developmental stages of the parasite life cycle. Detailed characterization of the enzymatic properties of telomerase using epimatigote-stage extract revealed a unique combination of substrate specificities, consistent with the evolutionary divergence of trypanosomes from previously established model systems for telomerase biochemical characterization. Results from partial purification of T.cruzi telomerase suggest that the catalytically active enzyme is a large ribonucleoprotein complex and that the internal RNA template has an atypical, cytosine-rich permutation. These results expand our understanding of telomerase enzymology and should encourage the development of parasite-specific telomerase inhibitors as a method for disease therapy.
Muñoz
Denise P
DP
Department of Molecular and Cell Biology, 16 Barker Hall, University of California at Berkeley, Berkeley, CA 94720-3204, USA. DPMunoz@lbl.gov
Collins
Kathleen
K
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D009711:Nucleotides / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry; D012261:Ribonucleoproteins / Q000737:chemistry; D013379:Substrate Specificity; D019098:Telomerase / Q000302:isolation & purification / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry; D013698:Templates, Genetic; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development
D017931:DNA Primers; D009711:Nucleotides; D009841:Oligonucleotides; D012261:Ribonucleoproteins; D019098:Telomerase