Author/Authors :
Henri G.A.M. van Luenen، نويسنده , , Carol Farris، نويسنده , , Sabrina Jan، نويسنده , , Paul-Andre Genest، نويسنده , , Pankaj Tripathi، نويسنده , , Arno Velds، نويسنده , , Ron M. Kerkhoven، نويسنده , , Marja Nieuwland، نويسنده , , Andrew Haydock، نويسنده , , Gowthaman Ramasamy، نويسنده , , Saara Vainio، نويسنده , , Tatjana Heidebrecht، نويسنده , , Anastassis Perrakis، نويسنده , , Ludo Pagie، نويسنده , , Bas van Steensel، نويسنده , , Peter J. Myler، نويسنده , , Piet Borst، نويسنده ,
Abstract :
Some Ts in nuclear DNA of trypanosomes and Leishmania are hydroxylated and glucosylated to yield base J (β-D-glucosyl-hydroxymethyluracil). In Leishmania, about 99% of J is located in telomeric repeats. We show here that most of the remaining J is located at chromosome-internal RNA polymerase II termination sites. This internal J and telomeric J can be reduced by a knockout of J-binding protein 2 (JBP2), an enzyme involved in the first step of J biosynthesis. J levels are further reduced by growing Leishmania JBP2 knockout cells in BrdU-containing medium, resulting in cell death. The loss of internal J in JBP2 knockout cells is accompanied by massive readthrough at RNA polymerase II termination sites. The readthrough varies between transcription units but may extend over 100 kb. We conclude that J is required for proper transcription termination and infer that the absence of internal J kills Leishmania by massive readthrough of transcriptional stops.
