We have expertise in the characterisation of non-canonical DNA structures and the way in which single-stranded DNA-binding proteins interact with these structures. We are particularly interested in DNA sequences composed of tandem repeats of a short motif of 2-6 nucleotides, also known as STR (for short tandem repeats). STR sequences may contribute to both genome stability and instability. Telomeres are an example of STR sequences that contribute to genome stability by protecting the ends of linear chromosomes in eukaryotes. Other STR sequences are involved in genome instability, notably those whose expansion leads to a wide range of neurogenerative diseases. Our aim is to unravel the structures formed by long STR sequences (telomeric and non-telomeric) and to understand how proteins interact with these structures. We are particularly interest in the Replication Protein A (RPA), a single-stranded DNA-binding trimeric complex required in replication, recombination and repair processes and also involved in DNA damage response.
Among non-canonical DNA structures are i-motifs.
I-motifs (intercalated-motifs) are four-stranded structures that rely on the pairing of hemi-protonated cytosines. In vitro, they form at acid pH; recently they have regained the interest of researcher for their potential formation in cells. We are partners in a joint project funded by the ANR that aims to investigate the biological relevance of i-motif DNA and its targeting (iCARE).