Format

Send to

Choose Destination
Mol Cell. 2016 Jan 7;61(1):161-9. doi: 10.1016/j.molcel.2015.10.038. Epub 2015 Nov 25.

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

Author information

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.

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

Comment in

PMID:
26626482
PMCID:
PMC4712188
DOI:
10.1016/j.molcel.2015.10.038
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center