2. Academic Validation
  3. PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells

PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells

  • Mol Cell. 2016 Jan 7;61(1):161-9. doi: 10.1016/j.molcel.2015.10.038.
Davide Schiavone 1,  Stanislaw K Jozwiakowski 2,  Marina Romanello 1,  Guillaume Guilbaud 1,  Thomas A Guilliam 2,  Laura J Bailey 2,  Julian E Sale 3,  Aidan J Doherty 4
Affiliations

Affiliations

  • 1 MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
  • 2 Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, BN1 9RQ, UK.
  • 3 MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. Electronic address: jes@mrc-lmb.cam.ac.uk.
  • 4 Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, BN1 9RQ, UK. Electronic address: ajd21@sussex.ac.uk.
PMID: 26626482 DOI: 10.1016/j.molcel.2015.10.038
Abstract

G quadruplexes (G4s) can present potent blocks to DNA replication. Accurate and timely replication of G4s in vertebrates requires multiple specialized DNA helicases and polymerases to prevent genetic and epigenetic instability. Here we report that PrimPol, a recently described primase-polymerase (PrimPol), plays a crucial role in the bypass of leading strand G4 structures. While PrimPol is unable to directly replicate G4s, it can bind and reprime downstream of these structures. Disruption of either the catalytic activity or zinc-finger of PrimPol results in extreme G4-dependent epigenetic instability at the BU-1 locus in avian DT40 cells, indicative of extensive uncoupling of the replicative helicase and polymerase. Together, these observations implicate PrimPol in promoting restart of DNA synthesis downstream of, but closely coupled to, G4 replication impediments.

Keywords

G quadruplexes; PrimPol; TLS; epigenetic instability; polymerase; primase; replication stalling; repriming.

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