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Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator ORC1/CDC6 and have identified replication origins, revealing that both localize to the boundaries of the transcription units. A remarkably small number of active origins is seen, whose spacing is greater than in any other eukaryote. We show that replication and transcription in T. brucei have a profound functional overlap, as reducing ORC1/CDC6 levels leads to genome-wide increases in mRNA levels arising from the boundaries of the transcription units. In addition, ORC1/CDC6 loss causes derepression of silent Variant Surface Glycoprotein genes, which are critical for host immune evasion.

Original publication

DOI

10.1016/j.celrep.2012.06.007

Type

Journal article

Journal

Cell Rep

Publication Date

26/07/2012

Volume

2

Pages

185 - 197

Keywords

Binding Sites, DNA Replication, Epistasis, Genetic, Gene Expression Regulation, Genome, Protozoan, Models, Biological, Origin Recognition Complex, Replication Origin, Sequence Analysis, DNA, Transcription, Genetic, Trypanosoma brucei brucei