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Article Dans Une Revue Cell Année : 2010

SnapShot: Homologous Recombination in DNA Double-Strand Break Repair

Gerard Mazón
Eleni Mimitou
  • Fonction : Auteur
Lorraine Symington
  • Fonction : Auteur

Résumé

O 6 -alkylG adducts are highly mutagenic due to their capacity to efficiently form O 6 -alkylG:T mispairs during replication, thus triggering G→A 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 -mG:T 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 -alkylG:T 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 -alkylG:T intermediate. In addition, in vitro, the eATL protein efficiently prevents binding of MutS to the O 6 -alkylG:T 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.

Dates et versions

hal-04306389 , version 1 (24-11-2023)

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Citer

Gerard Mazón, Eleni Mimitou, Lorraine Symington. SnapShot: Homologous Recombination in DNA Double-Strand Break Repair. Cell, 2010, 142 (4), pp.648.e1-648.e2. ⟨10.1016/j.cell.2010.08.006⟩. ⟨hal-04306389⟩
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