Antimutator role of DNA glycosylase MutY in pathogenic Neisseria species.
J Bacteriol
; 187(8): 2801-9, 2005 Apr.
Article
en En
| MEDLINE
| ID: mdl-15805527
ABSTRACT
Genome alterations due to horizontal gene transfer and stress constantly generate strain on the gene pool of Neisseria meningitidis, the causative agent of meningococcal (MC) disease. The DNA glycosylase MutY of the base excision repair pathway is involved in the protection against oxidative stress. MC MutY expressed in Escherichia coli exhibited base excision activity towards DNA substrates containing A7,8-dihydro-8-oxo-2'-deoxyguanosine and AC mismatches. Expression in E. coli fully suppressed the elevated spontaneous mutation rate found in the E. coli mutY mutant. An assessment of MutY activity in lysates of neisserial wild-type and mutY mutant strains showed that both MC and gonococcal (GC) MutY is expressed and active in vivo. Strikingly, MC and GC mutY mutants exhibited 60- to 140-fold and 20-fold increases in mutation rates, respectively, compared to the wild-type strains. Moreover, the differences in transitions and transversions in rpoB conferring rifampin resistance observed with the wild type and mutants demonstrated that the neisserial MutY enzyme works in preventing GC-->AT transversions. These findings are important in the context of models linking mutator phenotypes of disease isolates to microbial fitness.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Disparidad de Par Base
/
ADN Glicosilasas
/
Guanina
/
Neisseria
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Bacteriol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Noruega