PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication.

Julie Bianchi, Sean G Rudd, Stanislaw K Jozwiakowski, Laura J Bailey, Violetta Soura, Elaine Taylor, Irena Stevanovic, Andrew J Green, Travis H Stracker, Howard D Lindsay, Aidan J Doherty

Molecular cell 2013 Nov 21

filter terms:

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) light-damaged 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 η-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. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Julie Bianchi, Sean G Rudd, Stanislaw K Jozwiakowski, Laura J Bailey, Violetta Soura, Elaine Taylor, Irena Stevanovic, Andrew J Green, Travis H Stracker, Howard D Lindsay, Aidan J Doherty. PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication. Molecular cell. 2013 Nov 21;52(4):566-73