DNA polymerase ζ in DNA replication and repair.
Animals
Cell Death
/ radiation effects
Cellular Senescence
/ radiation effects
DNA Damage
DNA Repair
DNA Replication
/ radiation effects
DNA-Binding Proteins
/ deficiency
DNA-Directed DNA Polymerase
/ deficiency
Embryo, Mammalian
Genomic Instability
/ radiation effects
Humans
Mice
Saccharomyces cerevisiae
/ enzymology
Saccharomyces cerevisiae Proteins
/ genetics
Ultraviolet Rays
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
19 09 2019
19 09 2019
Historique:
accepted:
08
08
2019
revised:
24
07
2019
received:
18
06
2019
pubmed:
15
8
2019
medline:
18
12
2019
entrez:
15
8
2019
Statut:
ppublish
Résumé
Here, we survey the diverse functions of DNA polymerase ζ (pol ζ) in eukaryotes. In mammalian cells, REV3L (3130 residues) is the largest catalytic subunit of the DNA polymerases. The orthologous subunit in yeast is Rev3p. Pol ζ also includes REV7 subunits (encoded by Rev7 in yeast and MAD2L2 in mammalian cells) and two subunits shared with the replicative DNA polymerase, pol δ. Pol ζ is used in response to circumstances that stall DNA replication forks in both yeast and mammalian cells. The best-examined situation is translesion synthesis at sites of covalent DNA lesions such as UV radiation-induced photoproducts. We also highlight recent evidence that uncovers various roles of pol ζ that extend beyond translesion synthesis. For instance, pol ζ is also employed when the replisome operates sub-optimally or at difficult-to-replicate DNA sequences. Pol ζ also participates in repair by microhomology mediated break-induced replication. A rev3 deletion is tolerated in yeast but Rev3l disruption results in embryonic lethality in mice. Inactivation of mammalian Rev3l results in genomic instability and invokes cell death and senescence programs. Targeting of pol ζ function may be a useful strategy in cancer therapy, although chromosomal instability associated with pol ζ deficiency must be considered.
Identifiants
pubmed: 31410467
pii: 5549710
doi: 10.1093/nar/gkz705
pmc: PMC6895278
doi:
Substances chimiques
DNA-Binding Proteins
0
Saccharomyces cerevisiae Proteins
0
DNA-Directed DNA Polymerase
EC 2.7.7.7
REV3 protein, S cerevisiae
EC 2.7.7.7
REV3L protein, human
EC 2.7.7.7
REV3L protein, mouse
EC 2.7.7.7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
8348-8361Subventions
Organisme : NCI NIH HHS
ID : P01 CA193124
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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