RRC ID 53829
Author Takemoto N, Numata I, Su'etsugu M, Miyoshi-Akiyama T.
Title Bacterial EndoMS/NucS acts as a clamp-mediated mismatch endonuclease to prevent asymmetric accumulation of replication errors.
Journal Nucleic Acids Res
Abstract Mismatch repair (MMR) systems based on MutS eliminate mismatches originating from replication errors. Despite extensive conservation of mutS homologues throughout the three domains of life, Actinobacteria and some archaea do not have genes homologous to mutS. Here, we report that EndoMS/NucS of Corynebacterium glutamicum is the mismatch-specific endonuclease that functions cooperatively with a sliding clamp. EndoMS/NucS function in MMR was fully dependent on physical interaction between EndoMS/NucS and sliding clamp. A combination of endoMS/nucS gene disruption and a mutation in dnaE, which reduced the fidelity of DNA polymerase, increased the mutation rate synergistically and confirmed the participation of EndoMS in replication error correction. EndoMS specifically cleaved G/T, G/G and T/T mismatches in vitro, and such substrate specificity was consistent with the mutation spectrum observed in genome-wide analyses. The observed substrate specificity of EndoMS, together with the effects of endoMS gene disruption, led us to speculate that the MMR system, regardless of the types of proteins in the system, evolved to address asymmetrically occurring replication errors in which G/T mismatches occur much more frequently than C/A mismatches.
Volume 46(12)
Pages 6152-6165
Published 2018-7-6
DOI 10.1093/nar/gky481
PII 5033531
PMID 29878158
PMC PMC6159521
MeSH Actinobacteria / genetics Bacterial Proteins / metabolism Base Pair Mismatch* Corynebacterium glutamicum / enzymology* Corynebacterium glutamicum / genetics DNA Replication* DNA-Directed DNA Polymerase / metabolism Endodeoxyribonucleases / metabolism* Genes, Bacterial Mutation
IF 11.502
Times Cited 6
DNA material Genomic DNA of Thermococcus kodakarensis JCM 12380 T (JGD07705).