PCNA ubiquitination and REV1 define temporally distinct mechanisms for controlling translesion synthesis in the avian cell line DT40
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Translesion synthesis (TLS) is a potentially mutagenic method of bypassing DNA damage encountered during replication that requires the recruitment of specialized DNA polymerases to stalled replication forks or postreplicative gaps. Current models suggest that TLS is activated by monoubiquitination of the DNA sliding clamp PCNA. However, in higher organisms, fully effective TLS also requires a noncatalytic function of the Y family polymerase REV1. Using the genetically tractable chicken cell line DT40, we show that TLS at stalled replication forks requires that both the translesion polymerase-interaction domain and ubiquitin-binding domain in the C terminus of REV1 are intact. Surprisingly, however, PCNA ubiquitination is not required to maintain normal fork progression on damaged DNA. Conversely, PCNA ubiquitination is essential for filling postreplicative gaps. Thus, PCNA ubiquitination and REV1 play distinct roles in the coordination of DNA damage bypass that are temporally separated relative to replication fork arrest.
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Two models are proposed for TLS: at the blocked replication fork or via a post-replicative gap-filling mechanism.
“Two models are currently proposed for TLS: at the blocked replication fork or via a post-replicative gap-filling mechanism [8,9].”
From Gap-filling and bypass at the replication fork are both active mechanisms for tolerance of low-dose ultraviolet-induced DNA damage in the human genome (2014) · cites this paper as [9]
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- Authors
- Edmunds, C. E., Simpson, L. J., & Sale, J. E.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Sale, Julian E.
- ORCID
- Sale, Julian E.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 30
- Issue
- 4
- Pages
- 519-529
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2042488015
- Cited by
- 239
- References
- 55
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 8 · 2023: 13 · 2022: 8 · 2021: 11 · 2020: 4 · 2019: 9 · 2018: 9 · 2017: 18 · 2016: 18 · 2015: 16 · 2014: 11 · 2013: 14 · 2012: 26
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- translesion synthesis, PCNA ubiquitination, Rev1, DNA sliding clamp, Y-family DNA polymerases, DNA damage bypass, stalled replication forks, replication fork progression, DT40 cells
- MeSH terms
- Y-Family DNA Polymerases, Amino Acid Sequence, Animals, Cell Line, Chickens, DNA, DNA Damage, DNA Repair, DNA Replication, Epistasis, Genetic, Humans, Molecular Sequence Data, Mutagens, Nuclear Proteins, Nucleotidyltransferases, Ultraviolet Rays, 4-Nitroquinoline-1-oxide, Sequence Alignment, Proliferating Cell Nuclear Antigen, Ubiquitin
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