Trypanosoma brucei BRCA2 acts in a life cycle-specific genome stability process and dictates BRC repeat number-dependent RAD51 subnuclear dynamics
作者： Anna Trenaman , Claire Hartley , Marko Prorocic , Danielle G. Passos-Silva , Moniek van den Hoek
DOI: 10.1093/NAR/GKS1192
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摘要: Trypanosoma brucei survives in mammals through antigenic variation, which is driven by RAD51-directed homologous recombination of Variant Surface Glycoproteins (VSG) genes, most reside a subtelomeric repository >1000 silent genes. A key regulator RAD51 BRCA2, T. contains dramatic expansion motif that mediates interaction with RAD51, termed the BRC repeats. BRCA2 mutants were made both tsetse fly-derived and mammal-derived brucei, we show loss has less impact on health former. In addition, find genome instability, hallmark other organisms, only seen brucei. By generating cells expressing variants altered repeat numbers, crucial for subnuclear dynamics after DNA damage. Finally, document surprisingly limited co-localization nucleus, display aberrant cell division, revealing function distinct from BRC-mediated interaction. We propose acts to maintain huge VSG this necessitated evolution extensive via repeats, allowing re-localization recombinase general damage when needed.
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