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Cell Rep. 2017 Nov 7;21(6):1574-1587. doi: 10.1016/j.celrep.2017.10.039.

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

Author information

1
Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain. Electronic address: modesto.redrejo@csic.es.
2
Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain.
3
Institut Pasteur, Unité Biologie Moléculaire du Gène chez les Extrêmophiles, Paris, France.
4
Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain. Electronic address: msalas@cbm.csic.es.
5
Institut Pasteur, Unité Biologie Moléculaire du Gène chez les Extrêmophiles, Paris, France. Electronic address: krupovic@pasteur.fr.

Abstract

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.

KEYWORDS:

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

PMID:
29117562
PMCID:
PMC5695915
DOI:
10.1016/j.celrep.2017.10.039
[Indexed for MEDLINE]
Free PMC Article

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