PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication

Bianchi, Julie, Rudd, Sean G, Jozwiakowski, Stanislaw K, Bailey, Laura J, Soura, Violetta, Taylor, Elaine, Stevanovic, Irena, Green, Andrew J, Stracker, Travis H, Lindsay, Howard D and Doherty, Aidan J (2013) PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication. Molecular Cell, 52 (4). pp. 566-573. ISSN 1097-2765

[img]
Preview
PDF - Accepted Version
Download (5MB) | Preview

Abstract

DNA 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.

Item Type: Article
Additional Information: A.J.D. laboratory was supported by a project grant from BBSRC and a centre grant from the MRC.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Related URLs:
Depositing User: Deeptima Massey
Date Deposited: 28 Oct 2013 15:38
Last Modified: 08 Mar 2017 14:21
URI: http://sro.sussex.ac.uk/id/eprint/46833

View download statistics for this item

📧 Request an update