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Nucleic Acids Research Advance Access published online on January 9, 2009
Nucleic Acids Research, doi:10.1093/nar/gkn1067
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nucleic Acid Enzymes

JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes

Laura J. Cliffe, Rudo Kieft, Timothy Southern, Shanda R. Birkeland, Marion Marshall, Kate Sweeney and Robert Sabatini*

Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA

*To whom correspondence should be addressed. Tel: +1 706 542 9806; Fax: +1 508 289 1221; Email: rsabatini{at}bmb.uga.edu

Received November 25, 2008. Revised December 18, 2008. Accepted December 18, 2008.

Genomic DNA of African trypanosomes contains a hypermodified thymidine residue termed base J (β-D-glucosyl-HOMedU). This modified base is localized primarily to repetitive DNA, namely the telomeres, and is implicated in the regulation of antigenic variation. The base is synthesized in a two-step pathway. Initially, a thymidine residue in DNA is hydroxylated by a thymidine hydroxylase (TH). This intermediate (HOMedU) is then glucosylated to form base J. Two proteins involved in J synthesis, JBP1 (J binding protein 1) and JBP2, contain a putative TH domain related to the family of Fe2+/2-oxoglutarate-dependent hydroxylases. We have previously shown that mutations in the TH domain of JBP1 kill its ability to stimulate J synthesis. Here we show that mutation of key residues in the TH domain of JBP2 ablate its ability to induce de novo J synthesis. While the individual JBP1 null and JBP2 null trypanosomes have reduced J levels, the deletion of both JBP1 and JBP2 generates a cell line that completely lacks base J but still contains glucosyl-transferase activity. Reintroduction of JBP2 in the J-null trypanosome stimulates HOMedU formation and site-specific synthesis of base J. We conclude that JBP2 and JBP1 are the TH enzymes involved in J biosynthesis.


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