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Article Dans Une Revue Nucleic Acids Research Année : 2024

Correction of non-random mutational biases along a linear bacterial chromosome by the mismatch repair endonuclease NucS

Résumé

The linear chromosome of Streptomyces exhibits a highly compartmentalized structure with a conserved central region flanked by variable arms. As double strand break (DSB) repair mechanisms play a crucial role in shaping the genome plasticity of Streptomyces, we investigated the role of EndoMS/NucS, a recently characterized endonuclease involved in a non-canonical mismatch repair (MMR) mechanism in archaea and actinobacteria, that singularly corrects mismatches by creating a DSB. We showed that Streptomyces mutants lacking NucS display a marked colonial phenotype and a drastic increase in spontaneous mutation rate. In vitro biochemical assays revealed that NucS cooperates with the replication clamp to efficiently cleave G/T, G/G and T/T mismatched DNA by producing DSBs. These findings are consistent with the transition-shifted mutational spectrum observed in the mutant strains and reveal that NucS-dependent MMR specific task is to eliminate G/T mismatches generated by the DNA polymerase during replication. Interestingly, our data unveil a crescent-shaped distribution of the transition frequency from the replication origin towards the chromosomal ends, shedding light on a possible link between NucS-mediated DSBs and Streptomyces genome evolution.
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hal-04495979 , version 1 (12-03-2024)

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Oyut Dagva, Annabelle Thibessard, Jean-Noël Lorenzi, Victor Labat, Emilie Piotrowski, et al.. Correction of non-random mutational biases along a linear bacterial chromosome by the mismatch repair endonuclease NucS. Nucleic Acids Research, 2024, ⟨10.1093/nar/gkae132⟩. ⟨hal-04495979⟩
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