PT  - JOURNAL ARTICLE
AU  - Mehnert, Ann-Kathrin
AU  - Prorocic, Marco
AU  - Dujeancourt-Henry, Annick
AU  - Hutchinson, Sebastian
AU  - McCulloch, Richard
AU  - Glover, Lucy
TI  - RAD50 promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes
AID  - 10.1101/2020.03.17.994905
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.17.994905
4099  - http://biorxiv.org/content/early/2020/03/17/2020.03.17.994905.short
4100  - http://biorxiv.org/content/early/2020/03/17/2020.03.17.994905.full
AB  - 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.