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Mol Biochem Parasitol. 2014 Aug;196(1):9-11. doi: 10.1016/j.molbiopara.2014.07.005. Epub 2014 Jul 23.

Tb927.10.6900 encodes the glucosyltransferase involved in synthesis of base J in Trypanosoma brucei.

Author information

1
Seattle Biomedical Research Institute, 307 Westlake Avenue N., Seattle WA 98109-5219, USA.
2
Seattle Biomedical Research Institute, 307 Westlake Avenue N., Seattle WA 98109-5219, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
3
Seattle Biomedical Research Institute, 307 Westlake Avenue N., Seattle WA 98109-5219, USA; Department of Biomedical Informatics & Medical Education, Seattle, WA 98195, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA. Electronic address: peter.myler@seattlebiomed.org.

Abstract

Base J is a DNA modification found in the genome of Trypanosoma brucei and all other kinetoplastids analyzed, where it replaces a small fraction of Ts, mainly in telomeric and chromosome-internal transcription initiation and termination regions. The synthesis of base J is a two-step process whereby a specific T is converted to HOMedU (hydroxymethyldeoxyuridine) and subsequently glucosylated to generate J. The thymidine hydroxylases (JPB1 and JBP2) that catalyze the first step have been characterized, but the identity of the glucosyltransferase catalyzing the second step has proven elusive. Recent bioinformatic analysis by Iyer et al. (Nucleic Acids Res 2013;41:7635) suggested that Tb927.10.6900 encodes the glucosyltransferase (HmdUGT) responsible for converting HOMedU to J in T. brucei. We now present experimental evidence to validate this hypothesis; null mutants of Tb927.10.6900 are unable to synthesize base J. Orthologues from related kinetoplastids show only modest conservation, with several insertion sequences found in those from Leishmania and related genera.

KEYWORDS:

DNA modification; Epigenetics; Glucosyltransferase; Transcriptional read-through; Trypanosomatids

PMID:
25064607
PMCID:
PMC4206709
DOI:
10.1016/j.molbiopara.2014.07.005
[Indexed for MEDLINE]
Free PMC Article

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