Mechanisms of accurate translesion synthesis by human DNA polymerase η
Open accessAbstract
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta (pol eta), which is involved in the replication of damaged DNA. Pol eta catalyzes efficient and accurate translesion synthesis past cis-syn cyclobutane di-thymine lesions. Here we show that human pol eta can catalyze translesion synthesis past an abasic (AP) site analog, N-2-acetylaminofluorene (AAF)-modified guanine, and a cisplatin-induced intrastrand cross-link between two guanines. Pol eta preferentially incorporated dAMP and dGMP opposite AP, and dCMP opposite AAF-G and cisplatin-GG, but other nucleotides were also incorporated opposite these lesions. However, after incorporating an incorrect nucleotide opposite a lesion, pol eta could not continue chain elongation. In contrast, after incorporating the correct nucleotide opposite a lesion, pol eta could continue chain elongation, whereas pol alpha could not. Thus, the fidelity of translesion synthesis by human pol eta relies not only on the ability of this enzyme to incorporate the correct nucleotide opposite a lesion, but also on its ability to elongate only DNA chains that have a correctly incorporated nucleotide opposite a lesion.
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Polymerase η can also replicate across abasic sites, AAF, guanine adducts, and cis-platinated guanines.
“Polymerase η (pol. η) can also replicate across a basic sites, AAF (acetylaminofluorene), guanine adducts and cis-platinated guanines [352].”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [352]
The Abstract and translesion-synthesis assay passages report that human polymerase η bypassed an abasic-site analog, AAF-modified guanine, and a cisplatin cross-link between two guanines. The claim is broader than the tested substrates: the paper does not establish bypass of abasic sites themselves or guanine adducts as a general class. (LLM, conf=0.83)
Experimental — accuracy not yet measuredBypass of the most frequent UV lesions, TT-CPDs, by pol eta is error-free.
“While pol eta is an error-prone polymerase for some DNA lesions, the bypass of the most frequent UV lesions, TT-CPDs by pol eta is error free ( 7 ).”
From Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells (2017) · cites this paper as [7]
The Abstract describes efficient and accurate synthesis past cis-syn di-thymine lesions, and the translesion-synthesis section reports efficient bypass of a TT-CPD. But the paper also reports elongation from a mispaired primer on a CPD-containing template, so “error-free” overstates its finding of considerable accuracy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTranslesion synthesis past a CPD is facilitated by polymerase η, which inserts adenines opposite both bases of a T∧T CPD, whereas a 6-4TT lesion may lead to insertion of G.
“It has been reported that translesion synthesis past a CPD, facilitated by pol. η, with the insertion of adenines opposite both bases of a T∧T CPD [352], where as 6-4TT may lead to a G insertion.”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [352]
Polη ensures accurate replication of TT-CPDs, and its bypass may act at stalled replication forks and through post-replicative gap-filling.
“It is well established that Pol ensures accurate replication of TT-CPDs [21,22] and this bypass may act at the stalled replication fork [23,24] but also through a post-replicative gapfilling pathway [15,25].”
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 [21]
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- Authors
- Masutani, C., Kusumoto, R., Iwai, S., & Hanaoka, F.
- Affiliations
- The University of Osaka (JP)
- Biomolecular Engineering Research Institute (Japan) (JP)
- RIKEN (JP)
- Corresponding author
- Hanaoka, Fumio
- Venue
- The EMBO Journal
- Published
- 2000-06-15
- Volume
- 19
- Issue
- 12
- Pages
- 3100-3109
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC203367
- OpenAlex
- W1968679294
- Cited by
- 504
- References
- 54
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 14 · 2022: 8 · 2021: 11 · 2020: 17 · 2019: 12 · 2018: 16 · 2017: 11 · 2016: 14 · 2015: 19 · 2014: 11 · 2013: 15 · 2012: 23
- FWCI
- 12.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- RIKEN
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- DNA polymerase eta, translesion synthesis, xeroderma pigmentosum variant, DNA repair, abasic sites, N-2-acetylaminofluorene, cyclobutane pyrimidine dimers, replication fidelity, nucleotide incorporation, chain extension, DNA polymerase alpha
- MeSH terms
- DNA Polymerase iota, Y-Family DNA Polymerases, Deoxyribonucleotides, DNA Damage, DNA Polymerase I, DNA-Directed DNA Polymerase, DNA Replication, Guanine, Humans, Xeroderma Pigmentosum, Mutagenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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