title: PrimPol, an archaic primase/polymerase operating in human cells.
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.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: García-Gómez
authors.forename: Aurelio
authors.initials: A
authors.lastname: Reyes
authors.forename: María I
authors.initials: MI
authors.lastname: Martínez-Jiménez
authors.forename: E Sandra
authors.initials: ES
authors.lastname: Chocrón
authors.forename: Silvana
authors.initials: S
authors.lastname: Mourón
authors.forename: Gloria
authors.initials: G
authors.lastname: Terrados
authors.forename: Christopher
authors.initials: C
authors.lastname: Powell
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salido
authors.forename: Juan
authors.initials: J
authors.lastname: Méndez
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Holt
authors.forename: Luis
authors.initials: L
authors.lastname: Blanco
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001080:Apurinic Acid / Q000737:chemistry; D001483:Base Sequence; D020134:Catalytic Domain; D002467:Cell Nucleus / Q000201:enzymology; D004257:DNA Polymerase II / Q000737:chemistry; D000074002:DNA Polymerase gamma; D019915:DNA Primase / Q000737:chemistry / Q000502:physiology*; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000502:physiology*; D003839:Deoxyadenosines / Q000737:chemistry; D003854:Deoxyribonucleotides / Q000737:chemistry; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D064251:Multifunctional Enzymes / Q000737:chemistry / Q000502:physiology*
chemical_list: D004272:DNA, Mitochondrial; D004277:DNA, Single-Stranded; D003839:Deoxyadenosines; D003854:Deoxyribonucleotides; D064251:Multifunctional Enzymes; D001080:Apurinic Acid; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine; D019915:DNA Primase; C585901:PrimPol protein, human; D004257:DNA Polymerase II; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase