Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells
Open accessAbstract
Nucleotide excision repair (NER) is the most versatile DNA repair system that deals with the major UV photoproducts in DNA, as well as many other DNA adducts. The early steps of NER are well understood, whereas the later steps of repair synthesis and ligation are not. In particular, which polymerases are definitely involved in repair synthesis and how they are recruited to the damaged sites has not yet been established. We report that, in human fibroblasts, approximately half of the repair synthesis requires both pol kappa and pol delta, and both polymerases can be recovered in the same repair complexes. Pol kappa is recruited to repair sites by ubiquitinated PCNA and XRCC1 and pol delta by the classical replication factor complex RFC1-RFC, together with a polymerase accessory factor, p66, and unmodified PCNA. The remaining repair synthesis is dependent on pol epsilon, recruitment of which is dependent on the alternative clamp loader CTF18-RFC.
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DNA polymerase κ directly participates in NER repair synthesis in human cells, and loss of TLS activity greatly potentiates the checkpoint response to UV in yeast G1 cells, suggesting closely opposing UV lesions may be at least partly responsible for checkpoint activation.
“Interestingly, it was recently shown that DNA polymerase κ directly participates to NER repair synthesis in human cells [70,71] and that loss of TLS activity greatly potentiates the checkpoint response to UV irradiation in yeast G1 cells [61], suggesting that closely opposing UV lesions may indeed be at least partly responsible for checkpoint activation.”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [71]
In human cells, DNA polymerase κ is responsible for approximately 30% of unscheduled DNA synthesis detected in UV-irradiated cells.
“an unexpected role for TLS polymerases in NER was described in human cells, where DNA polymerase κ was found to be responsible for approximately 30% of the unscheduled DNA synthesis detected in UV-irradiated cells [70,71].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [71]
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Self-citation
- Authors
- Ogi, T., Limsirichaikul, S., Overmeer, R. M., Volker, M., Takenaka, K., Cloney, R., Nakazawa, Y., Niimi, A., Miki, Y., Jaspers, N. G., Mullenders, L. H. F., Yamashita, S., Fousteri, M. I., & Lehmann, A. R.
- Affiliations
- Nagasaki University (JP)
- Leiden University Medical Center (NL)
- University of Sussex (GB)
- Tokyo Medical and Dental University (JP)
- Erasmus MC (NL)
- Corresponding author
- Ogi, Tomoo
- Lehmann, Alan R.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 37
- Issue
- 5
- Pages
- 714-727
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2037936898
- Cited by
- 392
- References
- 55
- Citations by year
- 2026: 18 · 2025: 13 · 2024: 23 · 2023: 25 · 2022: 16 · 2021: 22 · 2020: 19 · 2019: 15 · 2018: 20 · 2017: 31 · 2016: 21 · 2015: 20 · 2014: 33 · 2013: 26 · 2012: 40
- FWCI
- 15.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (acceptedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Nagasaki University's Academic Output SITE (Nagasaki University) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- nucleotide excision repair, DNA repair synthesis, DNA polymerase kappa, DNA polymerase delta, DNA polymerase epsilon, PCNA ubiquitination, XRCC1, replication factor C, p66, UV photoproducts, human fibroblasts
- MeSH terms
- ATPases Associated with Diverse Cellular Activities, Poly-ADP-Ribose Binding Proteins, X-ray Repair Cross Complementing Protein 1, Y-Family DNA Polymerases, Carrier Proteins, Cell Line, DNA Damage, DNA Polymerase II, DNA Polymerase III, DNA-Directed DNA Polymerase, DNA Repair, DNA-Binding Proteins, Fibroblasts, Humans, Nuclear Proteins, Protein Processing, Post-Translational, Recombinant Fusion Proteins, Time Factors, Transfection, Ultraviolet Rays, Cellular Senescence, Proliferating Cell Nuclear Antigen, Protein Transport, RNA Interference, Ubiquitin-Protein Ligases, Replication Protein C, Ubiquitination
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