Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O6-alkylguanine adducts in Escherichia coli.
Proc Natl Acad Sci U S A
; 107(42): 18050-5, 2010 Oct 19.
Article
em En
| MEDLINE
| ID: mdl-20921378
ABSTRACT
O(6)-alkylG adducts are highly mutagenic due to their capacity to efficiently form O(6)-alkylGT mispairs during replication, thus triggering GâA transitions. Mutagenesis is largely prevented by repair strategies such as reversal by alkyltransferases or excision by nucleotide excision repair (NER). Moreover, methyl-directed mismatch repair (MMR) is known to trigger sensitivity to methylating agents via a mechanism that involves recognition by MutS of the O(6)-mGT replication intermediates. We wanted to investigate the mechanism by which MMR controls the genotoxicity of environmentally relevant O(6)-alkylG adducts formed by ethylene oxide and propylene oxide. Recently, the alkyltransferase-like gene ybaZ (eATL) was shown to enhance repair of these slightly larger O(6)-alkylG adducts by NER. We analyzed the toxicity and mutagenesis induced by these O(6)-alkylG adducts using single-adducted plasmid probes. We show that the eATL gene product prevents MMR-mediated attack of the O(6)-alkylGT replication intermediate for the larger alkyl groups but not for methyl. In vivo data are compatible with the occurrence of repeated cycles of MMR attack of the O(6)-alkylGT intermediate. In addition, in vitro, the eATL protein efficiently prevents binding of MutS to the O(6)-alkylGT mispairs formed by the larger alkyl groups but not by methyl. In conclusion, eATL not only enhances the efficiency of repair of these larger adducts by NER, it also shields these adducts from MMR-mediated toxicity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adutos de DNA
/
Alquil e Aril Transferases
/
Pareamento Incorreto de Bases
/
Proteínas de Escherichia coli
/
Reparo do DNA
/
Escherichia coli
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article