PrimPol, an archaic primase/polymerase operating in human cells

Mol Cell. 2013 Nov 21;52(4):541-53. doi: 10.1016/j.molcel.2013.09.025. Epub 2013 Oct 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apurinic Acid / chemistry
  • Base Sequence
  • Catalytic Domain
  • Cell Nucleus / enzymology
  • DNA Polymerase II / chemistry
  • DNA Polymerase gamma
  • DNA Primase / chemistry
  • DNA Primase / physiology*
  • DNA Replication*
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / genetics
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / physiology*
  • Deoxyadenosines / chemistry
  • Deoxyribonucleotides / chemistry
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Mitochondria / enzymology
  • Molecular Sequence Data
  • Multifunctional Enzymes / chemistry
  • Multifunctional Enzymes / physiology*

Substances

  • DNA, Mitochondrial
  • DNA, Single-Stranded
  • Deoxyadenosines
  • Deoxyribonucleotides
  • Multifunctional Enzymes
  • Apurinic Acid
  • 2'-deoxy-7,8-dihydro-8-oxoadenosine
  • DNA Polymerase II
  • DNA Primase
  • PrimPol protein, human
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase