PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells

Schiavone, Davide, Jozwiakowski, Stanislaw K, Romanello, Marina, Guilbaud, Guillaume, Guilliam, Thomas A, Bailey, Laura J, Sale, Julian E and Doherty, Aidan J (2016) PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells. Molecular Cell, 61 (1). pp. 161-169. ISSN 1097-2765

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Aidan Doherty
Date Deposited: 15 Jan 2016 13:40
Last Modified: 11 Sep 2017 05:55
URI: http://sro.sussex.ac.uk/id/eprint/59199

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Project NameSussex Project NumberFunderFunder Ref
The role of a novel family of eukaryotic DNA polymerases in mimitochondrial DNA replicationR3HABiotechnology and Biological Sciences Research CouncilBB/H019723/1
Understanding the role of PrimPol in damage tolerance during genome replication in eukaryotic cellsG1621-03Biotechnology and Biological Sciences Research CouncilBB/M008800/1