Primer-Independent DNA Synthesis by a Family B DNA Polymerase from Self-Replicating Mobile Genetic Elements

Modesto Redrejo-Rodríguez (1, 2) , Carlos Ordonez (1, 2) , Mónica Berjón-Otero (1, 2) , Juan Moreno-González (1, 2) , Cristian Aparicio-Maldonado (1, 2) , Patrick Forterre (3) , Margarita Salas (1, 2) , Mart Krupovic (3)

1 CBMSO - Centro de Biología Molecular Severo Ochoa [Madrid]
2 UAM - Universidad Autónoma de Madrid
3 BMGE - Biologie Moléculaire du Gène chez les Extrêmophiles

Family B DNA polymerases (PolBs) play a central role during replication of viral and cellular chromosomes. Here, we report the discovery of a third major group of PolBs, which we denote primer-independent PolB (piPolB), that might be a link between the previously known protein-primed and RNA/DNA-primed PolBs. PiPolBs are encoded by highly diverse mobile genetic elements, pipolins, integrated in the genomes of diverse bacteria and also present as circular plasmids in mitochondria. Biochemical characterization showed that piPolB displays efficient DNA polymerization activity that can use undamaged and damaged templates and is endowed with proofreading and strand displacement capacities. Remarkably, the protein is also capable of template-dependent de novo DNA synthesis, i.e., DNA-priming activity, thereby breaking the long-standing dogma that replicative DNA polymerases require a pre-existing primer for DNA synthesis. We suggest that piPolBs are involved in self-replication of pipolins and may also contribute to bacterial DNA damage tolerance.

Mots clés: DNA damage; DNA replication; de novo DNA synthesis; family B DNA polymerase; primer-independent DNA synthesis; self-replicating mobile element; translesion synthesis

Domaines: Sciences du Vivant [q-bio]; Génétique; Bactériologie

Modesto Redrejo-Rodríguez, Carlos Ordonez, Mónica Berjón-Otero, Juan Moreno-González, Cristian Aparicio-Maldonado, et al.. Primer-Independent DNA Synthesis by a Family B DNA Polymerase from Self-Replicating Mobile Genetic Elements. Cell Reports, 2017, 21 (6), pp.1574-1587. ⟨10.1016/j.celrep.2017.10.039⟩. ⟨pasteur-01977354⟩