Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania.

Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania.
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DOI:
10.1016/j.cell.2012.07.030
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发表时间:
2012-08-31
期刊:
影响因子:
64.5
通讯作者:
Borst P
Borst P
中科院分区:
生物学1区
文献类型:
--
作者:
van Luenen HG;Farris C;Jan S;Genest PA;Tripathi P;Velds A;Kerkhoven RM;Nieuwland M;Haydock A;Ramasamy G;Vainio S;Heidebrecht T;Perrakis A;Pagie L;van Steensel B;Myler PJ;Borst P

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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.
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