The MRN complex promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
22 02 2021
22 02 2021
Historique:
accepted:
22
12
2020
revised:
16
12
2020
received:
18
03
2020
pubmed:
16
1
2021
medline:
4
3
2021
entrez:
15
1
2021
Statut:
ppublish
Résumé
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 and MRE11 are required for RAD51-dependent homologous recombination and phosphorylation of histone H2A following a DNA double strand break (DSB), but neither MRE11 nor RAD50 substantially influence DSB resection at a chromosome-internal locus. In addition, we reveal intrinsic separation-of-function between T. brucei RAD50 and MRE11, with only RAD50 suppressing DSB repair using donors with short stretches of homology at a subtelomeric locus, and only MRE11 directing DSB resection at the same locus. Finally, we show that loss of either MRE11 or RAD50 causes a greater diversity of expressed VSG variants following DSB repair. We conclude that MRN promotes stringent homologous recombination at subtelomeric loci and restrains antigenic variation.
Identifiants
pubmed: 33450001
pii: 6101597
doi: 10.1093/nar/gkaa1265
pmc: PMC7897489
doi:
Substances chimiques
DNA-Binding Proteins
0
Protozoan Proteins
0
MRE11 Homologue Protein
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1436-1454Subventions
Organisme : Wellcome Trust
ID : 089172
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206815
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0401553
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K006495/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N016165/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104111
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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