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RAD50 promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes

Abstract : Homologous recombination dominates as the major form of DNA repair in Trypanosoma brucei , and is especially important for recombination of the subtelomeric variant surface glycoprotein during antigenic variation. RAD50, a component of the MRN complex (MRE11, RAD50, NBS1), is central to homologous recombination through facilitating resection and governing the DNA damage response. The function of RAD50 in trypanosomes is untested. Here we report that RAD50 is required for RAD51-dependent homologous recombination, phosphorylation of histone H2A and controlled resection following a DNA double strand break (DSB). Perhaps surprisingly, DSB resection in the rad50 nulls was not impaired and appeared to peak earlier than in the parental strains. Finally, we show that RAD50 suppresses DNA repair using donors with short stretches of homology at a subtelomeric locus, with null strains producing a greater diversity of expressed VSG variants following DSB repair. We conclude that RAD50 promotes stringent homologous recombination at subtelomeric loci and restrains antigenic variation.
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Preprints, Working Papers, ...
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03107143
Contributor : Lucy Glover <>
Submitted on : Tuesday, January 12, 2021 - 1:27:18 PM
Last modification on : Wednesday, January 20, 2021 - 3:42:05 PM
Long-term archiving on: : Tuesday, April 13, 2021 - 6:33:51 PM

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Ann-Kathrin Mehnert, Marco Prorocic, Annick Dujeancourt-Henry, Sebastian Hutchinson, Richard Mcculloch, et al.. RAD50 promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes. 2021. ⟨pasteur-03107143⟩

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