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

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journal contribution
posted on 2023-06-12, 06:36 authored by Davide Schiavone, Stanislaw K Jozwiakowski, Marina Romanello, Guillaume Guilbaud, Thomas A Guilliam, Laura BaileyLaura Bailey, Julian E Sale, Aidan DohertyAidan Doherty
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.

Funding

The role of a novel family of eukaryotic DNA polymerases in mimitochondrial DNA replication; R3HA; Biotechnology and Biological Sciences Research Council; BB/H019723/1

Understanding the role of PrimPol in damage tolerance during genome replication in eukaryotic cells; G1621-03; Biotechnology and Biological Sciences Research Council; BB/M008800/1

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular Cell

ISSN

1097-2765

Publisher

Elsevier

Issue

1

Volume

61

Page range

161-169

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-15

First Open Access (FOA) Date

2016-01-15

First Compliant Deposit (FCD) Date

2016-01-15

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