The Protein That Binds to DNA Base J in Trypanosomatids Has Features of a Thymidine Hydroxylase

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2007 Mar 29

PMID 17389644

Citations 46

Authors

Zhong Yu

Paul-Andre Genest

Bas Ter Riet

Kate Sweeney

Courtney DiPaolo

Rudo Kieft

Evangelos Christodoulou

Anastassis Perrakis

Jana M Simmons

Robert P Hausinger

Henri G A M van Luenen

Daniel J Rigden

Robert Sabatini

Piet Borst

Affiliations

Soon will be listed here.

Abstract

Trypanosomatids contain an unusual DNA base J (beta-d-glucosylhydroxymethyluracil), which replaces a fraction of thymine in telomeric and other DNA repeats. To determine the function of base J, we have searched for enzymes that catalyze J biosynthesis. We present evidence that a protein that binds to J in DNA, the J-binding protein 1 (JBP1), may also catalyze the first step in J biosynthesis, the conversion of thymine in DNA into hydroxymethyluracil. We show that JBP1 belongs to the family of Fe(2+) and 2-oxoglutarate-dependent dioxygenases and that replacement of conserved residues putatively involved in Fe(2+) and 2-oxoglutarate-binding inactivates the ability of JBP1 to contribute to J synthesis without affecting its ability to bind to J-DNA. We propose that JBP1 is a thymidine hydroxylase responsible for the local amplification of J inserted by JBP2, another putative thymidine hydroxylase.

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