RT Journal Article
T1 Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair
A1 Cebrián-Sastre, Esmeralda
A1 Martín-Blecua, Isabel
A1 Gullón, Sonia
A1 Blázquez, Jesús
A1 Castañeda-García, Alfredo
K1 EndoMS/NucS
K1 Non-canonical mismatch repair
K1 Genome stability
K1 Hypermutation
K1 Antibiotic resistance
K1 Actinobacteria
K1 Mycobacterium tuberculosis
K1 Reparación de la incompatibilidad de ADN
K1 Inestabilidad genómica
K1 Farmacorresistencia microbiana
K1 Actinobacteria
K1 ADN
K1 Mutación
AB The DNA repair endonuclease EndoMS/NucS is highly conserved in Archaea and Actinobacteria. This enzyme is able to recognize and cleave dsDNA carrying a mismatched base pair, and its activity is enhanced by the interaction with the sliding clamp of the replisome. Today, EndoMS/NucS has been established as the key protein of a non-canonical mismatch repair (MMR) pathway, acting specifically in the repair of transitions and being essential for maintaining genome stability. Despite having some particularities, such as its lower activity on transversions and the inability to correct indels, EndoMS/NucS meets the main hallmarks of a MMR. Its absence leads to a hypermutator phenotype, a transition-biased mutational spectrum and an increase in homeologous recombination. Interestingly, polymorphic EndoMS/NucS variants with a possible effect in mutation rate have been detected in clinical isolates of the relevant actinobacterial pathogen Mycobacterium tuberculosis. Considering that MMR defects are often associated with the emergence of resistant bacteria, the existence of EndoMS/NucS-defective mutators could have an important role in the acquisition of antibiotic resistance in M. tuberculosis. Therefore, a further understanding of the EndoMS/NucS-mediated non-canonical MMR pathway may reveal new strategies to predict and fight drug resistance. This review is focused on the recent progress in NucS, with special emphasis on its effect on genome stability and evolvability in Actinobacteria.
PB MDPI
YR 2021
FD 2021-05-25
LK http://hdl.handle.net/10668/4426
UL http://hdl.handle.net/10668/4426
LA en
NO Cebrián-Sastre E, Martín-Blecua I, Gullón S, Blázquez J, Castañeda-García A. Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair. Cells. 2021 May 25;10(6):1314
DS RISalud
RD Apr 6, 2025