Inactivation of Mre11 does not affect VSG gene duplication mediated by homologous recombination in Trypanosoma brucei.
We demonstrate, by gene deletion analysis, that Mre11 has a critical role in maintaining genomic integrity in Trypanosoma brucei. mre11(-/-) null mutant strains exhibited retarded growth but no delay or disruption of cell cycle progression. They showed also a weak hyporecombination phenotype and the accumulation of gross chromosomal rearrangements, which did not involve sequence translocation, telomere loss, or formation of new telomeres. The trypanosome mre11(-/-) strains were hypersensitive to phleomycin, a mutagen causing DNA double strand breaks (DSBs) but, in contrast to mre11(-/-) null mutants in other organisms and T. brucei rad51(-/-) null mutants, displayed no hypersensitivity to methyl methanesulfonate, which causes point mutations and DSBs. Mre11 therefore is important for the repair of chromosomal damage and DSBs in trypanosomes, although in this organism the intersection of repair pathways appears to differ from that in other organisms. Mre11 inactivation appears not to affect VSG gene switching during antigenic variation of a laboratory strain, which is perhaps surprising given the importance of homologous recombination during this process.
Robinson
Nicholas P
NP
Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, Scotland, United Kingdom.
McCulloch
Richard
R
Conway
Colin
C
Browitt
Alison
A
Barry
J David
JD
D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis; D004249:DNA Damage; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D020440:Gene Duplication / Q000187:drug effects*; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D010641:Phenotype; D010692:Phleomycins / Q000494:pharmacology; D017354:Point Mutation; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000235:genetics*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics*; D014982:Xenopus laevis
D010692:Phleomycins; D029701:Saccharomyces cerevisiae Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; D008741:Methyl Methanesulfonate; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae