PrimPol, an Archaic Primase/Polymerase Operating in Human Cells

Sara García-Gómez, Aurelio Reyes, María I. Martínez-Jiménez, E. Sandra Chocrón, Silvana Mourón, Gloria Terrados, Christopher Powell, Eduardo Salido, Juan Méndez, Ian J. Holt, Luis Blanco

Research output: Contribution to journalArticlepeer-review

305 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)541-553
Number of pages13
JournalMolecular Cell
Volume52
Issue number4
DOIs
StatePublished - Nov 21 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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