title: The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase.
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.
authors: Division of Molecular Biology and Centre of Biomedical Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors: Zhong
authors: Z
authors: Yu
authors: Paul-André
authors: PA
authors: Genest
authors: Bas
authors: B
authors: ter Riet
authors: Kate
authors: K
authors: Sweeney
authors: Courtney
authors: C
authors: DiPaolo
authors: Rudo
authors: R
authors: Kieft
authors: Evangelos
authors: E
authors: Christodoulou
authors: Anastassis
authors: A
authors: Perrakis
authors: Jana M
authors: JM
authors: Simmons
authors: Robert P
authors: RP
authors: Hausinger
authors: Henri G A M
authors: HG
authors: van Luenen
authors: Daniel J
authors: DJ
authors: Rigden
authors: Robert
authors: R
authors: Sabatini
authors: Piet
authors: P
authors: Borst
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D049308:Dioxygenases / Q000145:classification; D005960:Glucosides / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D007891:Leishmania / Q000235:genetics; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D014498:Uracil / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D005960:Glucosides; C402790:J-specific DNA-binding protein, protozoa; D015800:Protozoan Proteins; C084880:5-((glucopyranosyloxy)methyl)uracil; D014498:Uracil; D006899:Mixed Function Oxygenases; D049308:Dioxygenases; C023162:thymidine,2-oxoglutarate dioxygenase