J_Bianchi_PrimPol_bypasses_2013.pdf (5.64 MB)
PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication
journal contribution
posted on 2023-06-08, 16:12 authored by Julie Bianchi, Sean G Rudd, Stanislaw K Jozwiakowski, Laura BaileyLaura Bailey, Violetta Soura, Elaine Taylor, Irena Stevanovic, Andrew J Green, Travis H Stracker, Howard D Lindsay, Aidan DohertyAidan DohertyDNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) lightdamaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol h-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells.
History
Publication status
- Published
File Version
- Accepted version
Journal
Molecular CellISSN
1097-2765Publisher
ElsevierExternal DOI
Issue
4Volume
52Page range
566-573Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Notes
A.J.D. laboratory was supported by a project grant from BBSRC and a centre grant from the MRC.Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2013-10-28First Open Access (FOA) Date
2013-11-29First Compliant Deposit (FCD) Date
2013-11-29Usage metrics
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