PhD Marion Tassoni - Nucléase HAN : caractérisation de son réseau d'interactions moléculaires et de son rôle chez les Archées hyperthermophiles

This thesis focuses on HAN, a member of the DHH superfamily, initially proposed to participate in DNA replication fork restart through its interaction with HEF, a DNA helicase/endonuclease. However, our recent findings revealed that HAN also interacts with RNA metabolic players, raising questions about its dual role in DNA and RNA metabolism. To address this, we investigated the physiological, molecular, and functional interactions of HAN in T. barophilus. We first demonstrate HAN’s 3′–5′ exonuclease activity on single-stranded DNA and RNA, as well as its ability to displace DNA/RNA hybrids. We then characterized HAN’s in vitro and in vivo partners, revealing potential links to DNA repair and translation. To decipher HAN’s role in Archaea, we investigated the impact of its deletion on growth, cell morphology, RNA levels, and DNA/RNA hybrid accumulation under optimal and challenging conditions. Our findings suggest that HAN is recruited to conflict sites to resolve secondary structures by processing nucleic acids, positioning HAN as a key player at the intersection of informational processing machineries.