ARCREP

DNA repair is critical for the maintenance of genome integrity and replication fidelity in all cells. Archaea, and hyperthermophiles in particular, are well suited for studying DNA repair mechanisms given that DNA exposed to high temperature is subject to ongoing damage during normal growth under extreme conditions. Yet, recent work suggests that the mutation rates of model hyperthermophiles are quite close to norms for bacteria, indicating that their replication/repair processes are operating with high fidelity at elevated temperatures. In addition, using comparative genomic analysis and the genome sequence of several hyperthermophilic archaea, homologs of conserved eukaryotic and bacterial DNA repair proteins have been identified. However, many highly conserved repair genes are missing in some or in all of the archaeal genomes. Using a combinatorial approach of pull-down analyses coupled with mass spectrometry we have identified in Pyrococcus abyssi a network involved in genome maintenance mechanisms. This interaction network consists of at least two distinct functional modules required for DNA replication and/or repair of nucleic acid damage and is composed of novel protein complexes with likely new functions in DNA repair. this program aims to elucidate the biological functions of these novel complexes presumably involved in replication-coupled DNA repair in the hyperthermophilic archaeon Pyrococcus abyssi and to contribute to a better understanding of the molecular mechanisms involved in the interplay between DNA replication and DNA repair in archaea. This will be achieved through the coordination of chemical, biochemical, genetic and crystallographic approaches, to further characterise how the protein complexes are formed and what is their functional significance in DNA repair processes.