A distinct physiological role of MutY in mutation prevention in mycobacteria.
Microbiology (Reading)
; 156(Pt 1): 88-93, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-19778963
ABSTRACT
Oxidative damage to DNA results in the occurrence of 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. In eubacteria, repair of such damage is initiated by two major base-excision repair enzymes, MutM and MutY. We generated a MutY-deficient strain of Mycobacterium smegmatis to investigate the role of this enzyme in DNA repair. The MutY deficiency in M. smegmatis did not result in either a noteworthy susceptibility to oxidative stress or an increase in the mutation rate. However, rifampicin-resistant isolates of the MutY-deficient strain showed distinct mutations in the rifampicin-resistance-determining region of rpoB. Besides the expected C to A (or G to T) mutations, an increase in A to C (or T to G) mutations was also observed. Biochemical characterization of mycobacterial MutY (M. smegmatis and M. tuberculosis) revealed an expected excision of A opposite 8-oxoG in DNA. Additionally, excision of G and T opposite 8-oxoG was detected. MutY formed complexes with DNA containing 8-oxoG A, 8-oxoG G or 8-oxoG T but not 8-oxoG C pairs. Primer extension reactions in cell-free extracts of M. smegmatis suggested error-prone incorporation of nucleotides into the DNA. Based on these observations, we discuss the physiological role of MutY in specific mutation prevention in mycobacteria.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Mycobacterium smegmatis
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DNA Glicosilases
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Reparo do DNA
Limite:
Animals
Idioma:
En
Revista:
Microbiology (Reading)
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Índia