External Seminar : Carole SAINTOME

Eric GILSON invites: Carole SAINTOME – SANTE team (Structures des acides nucléiques, télomères, évolution) Structure et Instabilité des génomes, Muséum national d’Histoire naturelle – CNRS 9796, INSERM U1154, Sorbonne université

« The role of Single-Stranded DNA Binding proteins in telomeres maintenance« 

 Abstract: Telomeres are specialized DNA–protein structures that protect the ends of chromosomes and distinguish natural chromosome termini from unnatural breaks produced by DNA damage. They contain G-rich sequences that are able to adopt higher-order structures formed by contiguous G-quadruplexes (G4); these structures need to be unfolded to facilitate DNA replication and telomerase activity. Our team is interested in two single-stranded DNA binding proteins (SSBPs) essential in telomeres biology and able to unfold G4: the replication protein A (RPA), the major eukaryote SSBP, and the POT1 protein, the telomeric SSBP.

To understand the interplay of both proteins at telomeres, we used a set of biochemical and biophysical experiments to investigate the mechanism of G4 unfolding by RPA and POT1. Our data showed that RPA and POT1 open G4s with different mechanisms, suggesting a distinct role at telomeres.

Recently, we investigated RPA mutations present in telomere biology disorders (TBDs) patients, a group of rare and heterogeneous diseases characterized by premature telomere shortening and genomic instability. Our data link RPA mutations to TBDs.