PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication.
Mol Cell
; 52(4): 566-73, 2013 Nov 21.
Article
in En
| MEDLINE
| ID: mdl-24267451
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) 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomes, Human
/
DNA Adducts
/
DNA Primase
/
DNA-Directed DNA Polymerase
/
DNA Replication
/
Multifunctional Enzymes
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2013
Type:
Article
Affiliation country:
United kingdom