The base excision repair (BER) pathway is the main pathway for the repair of DNA base damage and single strand breaks. These kinds of lesions are generated continuously at high levels in every cells due to the normal metabolism, but their number is highly increased in cells exposed to oxidative stress conditions such as those encountered in pathologies including cancer, neurodegenerative diseases and inflammation. High levels of oxidative DNA damage are also produced in cells exposed to genetoxics such as ionizing radiation and a large number of industrial compounds and therapeutic drugs

Thus BER is a major barrier to prevent accumulation of DNA lesions therefore protecting against cell death or mutagenesis. Base excision repair of modified bases is initiated by lesion-specific DNA glycosylases. After oxidative stress, one of the main base lesions formed in DNA is 8-oxoguanine (8-oxoG) that, if left unrepaired, induces mutations potentially involved in cancer and aging. OGG1 is the major DNA glycoylase responsible for the removal of 8-oxoG.

​Mitochondria being the main producers of reactive oxygen species in the cell,  mitochondrial genome is particularly exposed to oxidation. Oxidative damage to mitochondrial DNA has been implicated in human degenerative diseases, tumorigenesis and aging. It is now clear that BER is the main pathway involved in the removal of these lesions. Interestingly, all the proteins involved in BER are encoded by the nuclear genome and the mechanism responsible for the targeting of the translated protein to the nucleus or to the mitochondria have not been clearly established yet. Different mechanism including alternative splicing, alternative transcription start or dual initiation of translation, have been proposed for different BER proteins. We are presently trying to understand what mechanisms regulate the targeting of the DNA glycosylases, in particular OGG1, to the mitochondria and how BER is coordinated in this organelle. 

More recently we have also established that unexpected factors such as the cellular prion protein can stimulate BER and we are now trying to identify the underlying mechanisms and the possible physiological implications of this response. 

Helicobacter pylori chronically colonises approximately half of the world’s population. Trans​mission between humans is thought to occur via person-to-person contact during childhood. Persistent infection is usually asymptomatic but can evolve in peptic ulcer disease and gastric cancer. Eradication treatments are based on antibiotics utilization, but during the last decade, H. pylori antibiotic resistance has increased dramatically. Up to 30% of patients are not cured after completing their first course of treatment. This augmentation, as well as the success in infection can be explained by the high adaptability of these bacteria. H. pylori is indeed one of the most genetically diverse bacteria and comparison of the sequenced genomes reveals an amazing variability between strains. This genomic variability is the result of high mutation rates, high recombination efficiency, and natural competence, which allows constant and rapid spread of new mutation among the bacterial population. There is therefore a critical balance between the maintenance of the genetic information and the capacity to adapt. 

Since 1999 our laboratory has contributed to the understanding of the DNA metabolism processes defining the genomic plasticity of H. pylori. Initially, the group has analysed both, biochemically and genetically, the Base Excision Repair pathway, unveiling a new family of DNA glycosylases. Since 2005, the LRIG has turned its attention to the study of Homologous Recombination (HR) in H. pylori allowing the identification of missing components of the mediator complexes responsible for the formation of an active RecA nucleofilament. Homologous recombination being the last step required for the integration of exogenous DNA into the bacterial chromosome, the LRIG has also extended its interests to the analysis of natural transformation in this pathogen. H. pylori presents several important differences with the other competent bacteria starting by the proteins involved in its transport across the two membranes to the fact that in this species natural competence is constitutive. By combining genetics, biochemistry and cell biology approaches we aim at understanding the molecular mechanisms by which the incoming DNA is processed first during its passage through the periplasm and then in the cytoplasm to recombine with the host genome.