DNA repair in prokaryotes

People involved:

• Hannu MYLLYKALLIO, DR, CNRS
• Stephane SKOULOUBRIS, MdC, Univ. Paris–Saclay
• Rima Zein-Eddine, Post-doc 'Marie Sklodowska-Curie' fellow '
• Amandine Ignace, AI
• Wenlu Yin, Doctorant

Topic:

DNA repair systems help maintain the integrity of genomes and therefore play a key role at both the cellular level and in the transmission of a faithful genetic inheritance to offspring. 

We are particularly interested in a protein called NucS (also known as EndoMS in the literature). The presence of this protein, discovered in the laboratory, is limited to the prokaryotic world. It is found in some species of Archaea (Crenarcheota and Euryarcheota) and in many bacteria belonging to the large phylum Actinobacteria (e.g. Corynebacteria and Mycobacteria). It exhibits cleavage activity against a variety of DNA substrates and is primarily involved in the detection and repair of mismatches.

Work is currently being undertaken within our team to better understand the mechanism by which NucS is involved in this repair. Two bacterial models are being studied in the lab: Corynebacterium glutamicum and Mycobacterium smegmatis. Various interdisciplinary approaches including molecular biology, genetics, biochemistry, microscopy and bioinformatics are used.

It has already been shown that NucS interacts with the protein known as beta-clamp (i.e. PCNA in archaea and DnaN in bacteria). Part of the project is therefore aimed at identifying and characterizing other partner proteins involved in this repair pathway. A second part of our work is focused on assessing the impact of mutations in the nucS gene on antibiotic resistance, which has been detected in numerous clinical isolates of the tuberculosis etiologic agent, Mycobacterium tuberculosis.