PrimPol Bypasses UV Photoproducts during Eukaryotic Chromosomal DNA Replication
| Autor: | Howard D. Lindsay, Andrew J. Green, Irena Stevanovic, Aidan J. Doherty, Sean G. Rudd, Elaine M. Taylor, Julie Bianchi, Laura J. Bailey, Stanislaw K. Jozwiakowski, Violetta Soura, Travis H. Stracker |
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| Rok vydání: | 2013 |
| Předmět: |
DNA Replication
Genome instability Cell Survival Ultraviolet Rays DNA damage Xenopus Molecular Sequence Data DNA Single-Stranded Eukaryotic DNA replication DNA Primase DNA-Directed DNA Polymerase Biology DNA Adducts Mice chemistry.chemical_compound Short Article Minichromosome maintenance Animals Chromosomes Human Humans Amino Acid Sequence Molecular Biology Cell Proliferation Mice Knockout Genetics DNA replication Cell Biology Multifunctional Enzymes G2 Phase Cell Cycle Checkpoints HEK293 Cells chemistry Gene Knockdown Techniques Origin recognition complex Primase Chickens DNA DNA Damage |
| Zdroj: | Molecular Cell |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2013.10.035 |
| Popis: | Summary 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. Graphical Abstract Highlights • PrimPol is a DNA primase-polymerase catalyzing bypass of UV and oxidative lesions • PrimPol operates in a UV lesion tolerance pathway that is non-epistatic with Pol η • PrimPol null cells are defective in fork progression, particularly after UV treatment • Loss of PrimPol leads to increased mitotic chromosomal breaks |
| Databáze: | OpenAIRE |
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