PrimPol, an archaic primase/polymerase operating in human cells.

TitlePrimPol, an archaic primase/polymerase operating in human cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsGarcía-Gómez, S, Reyes, A, Martínez-Jiménez, MI, E Chocrón, S, Mourón, S, Terrados, G, Powell, C, Salido, E, Méndez, J, Holt, IJ, Blanco, L
JournalMol Cell
Volume52
Issue4
Pagination541-53
Date Published2013 Nov 21
ISSN1097-4164
KeywordsAmino Acid Sequence, Animals, Apurinic Acid, Base Sequence, Catalytic Domain, Cell Nucleus, Deoxyadenosines, Deoxyribonucleotides, DNA Polymerase II, DNA Primase, DNA Replication, DNA, Mitochondrial, DNA, Single-Stranded, DNA-Directed DNA Polymerase, HEK293 Cells, HeLa Cells, Humans, Mice, Mice, Knockout, Mitochondria, Molecular Sequence Data, Multifunctional Enzymes
Abstract

We describe a second primase in human cells, PrimPol, which has the ability to start DNA chains with deoxynucleotides unlike regular primases, which use exclusively ribonucleotides. Moreover, PrimPol is also a DNA polymerase tailored to bypass the most common oxidative lesions in DNA, such as abasic sites and 8-oxoguanine. Subcellular fractionation and immunodetection studies indicated that PrimPol is present in both nuclear and mitochondrial DNA compartments. PrimPol activity is detectable in mitochondrial lysates from human and mouse cells but is absent from mitochondria derived from PRIMPOL knockout mice. PRIMPOL gene silencing or ablation in human and mouse cells impaired mitochondrial DNA replication. On the basis of the synergy observed with replicative DNA polymerases Polγ and Polε, PrimPol is proposed to facilitate replication fork progression by acting as a translesion DNA polymerase or as a specific DNA primase reinitiating downstream of lesions that block synthesis during both mitochondrial and nuclear DNA replication.

DOI10.1016/j.molcel.2013.09.025
Alternate JournalMol. Cell
Citation Key10.1016/j.molcel.2013.09.025
PubMed ID24207056
PubMed Central IDPMC3899013
Grant ListMC_UP_1202/14 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom