ArticlePloS one2015
Relevance of simultaneous mono-ubiquitinations of multiple units of PCNA homo-trimers in DNA damage tolerance.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Overlapping RAD18-and DNA-binding interfaces in DNA polymerase η contribute to UV-induced DNA damage tolerance.The Journal of biological chemistry · 2026Article
- Functional asymmetry in processivity clamp proteins.Biophysical journal · 2025Review
- Novel mechanisms for the removal of strong replication-blocking HMCES- and thiazolidine-DNA adducts in humans.Nucleic acids research · 2023Article
- RFWD3 and translesion DNA polymerases contribute to PCNA modification-dependent DNA damage tolerance.Life science alliance · 2022Article
- TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51Cell reports · 2020Article
- Regulation of HLTF-mediated PCNA polyubiquitination by RFC and PCNA monoubiquitination levels determines choice of damage tolerance pathway.Nucleic acids research · 2018Article
- Review
- Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA.Scientific reports · 2015Article
- Different types of interaction between PCNA and PIP boxes contribute to distinct cellular functions of Y-family DNA polymerases.Nucleic acids research · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage tolerance (DDT) pathways, including translesion synthesis (TLS) and additional unknown mechanisms, enable recovery from replication arrest at DNA lesions. DDT pathways are regulated by post-translational modifications of proliferating cell nuclear antigen (PCNA) at its K164 residue. In particular, mono-ubiquitination by the ubiquitin ligase RAD18 is crucial for Polη-mediated TLS. Although the importance of modifications of PCNA to DDT pathways is well known, the relevance of its homo-trimer form, in which three K164 residues are present in a single ring, remains to be elucidated. Here, we show that multiple units of a PCNA homo-trimer are simultaneously mono-ubiquitinated in vitro and in vivo. RAD18 catalyzed sequential mono-ubiquitinations of multiple units of a PCNA homo-trimer in a reconstituted system. Exogenous PCNA formed hetero-trimers with endogenous PCNA in WI38VA13 cell transformants. When K164R-mutated PCNA was expressed in these cells at levels that depleted endogenous PCNA homo-trimers, multiple modifications of PCNA complexes were reduced and the cells showed defects in DDT after UV irradiation. Notably, ectopic expression of mutant PCNA increased the UV sensitivities of Polη-proficient, Polη-deficient, and REV1-depleted cells, suggesting the disruption of a DDT pathway distinct from the Polη- and REV1-mediated pathways. These results suggest that simultaneous modifications of multiple units of a PCNA homo-trimer are required for a certain DDT pathway in human cells.
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