ArticleNucleic acids research2017
A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Exploiting DNA damage tolerance for precision oncology.Trends in cancer · 2026Review
- Mechanistic diversity of clamp loading at small DNA gaps.The Journal of biological chemistry · 2026Review
- Pds5 regulates sister chromatid cohesion by controlling cohesin ATPase activity through the Eco1-Smc3 acetylation pathway.Nucleic acids research · 2026Article
- A transient mutational burst occurs during yeast colony development.Molecular systems biology · 2025Article
- Interstitial telomeric sequences promote gross chromosomal rearrangement via multiple mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader.Nature structural & molecular biology · 2024Article
- Effects of PCNA Stability on the Formation of Mutations.International journal of molecular sciences · 2024Article
- PCNA Unloading Is Crucial for the Bypass of DNA Lesions Using Homologous Recombination.International journal of molecular sciences · 2024Article
- Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review.BMC medical genomics · 2024Article
- Short-range end resection requires ATAD5-mediated PCNA unloading for faithful homologous recombination.Nucleic acids research · 2023Article
- Article
- Effects of Defective Unloading and Recycling of PCNA Revealed by the Analysis ofInternational journal of molecular sciences · 2023Article
- Review
- Rad53 arrests leading and lagging strand DNA synthesis via distinct mechanisms in response to DNA replication stress.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Article
- Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice.Journal of fungi (Basel, Switzerland) · 2022Review
- Article
- Review
- Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair.Nucleic acids research · 2021Article
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The sliding clamp, PCNA, plays a central role in DNA replication and repair. In the moving replication fork, PCNA is present at the leading strand and at each of the Okazaki fragments that are formed on the lagging strand. PCNA enhances the processivity of the replicative polymerases and provides a landing platform for other proteins and enzymes. The loading of the clamp onto DNA is performed by the Replication Factor C (RFC) complex, whereas its unloading can be carried out by an RFC-like complex containing Elg1. Mutations in ELG1 lead to DNA damage sensitivity and genome instability. To characterize the role of Elg1 in maintaining genomic integrity, we used homology modeling to generate a number of site-specific mutations in ELG1 that exhibit different PCNA unloading capabilities. We show that the sensitivity to DNA damaging agents and hyper-recombination of these alleles correlate with their ability to unload PCNA from the chromatin. Our results indicate that retention of modified and unmodified PCNA on the chromatin causes genomic instability. We also show, using purified proteins, that the Elg1 complex inhibits DNA synthesis by unloading SUMOylated PCNA from the DNA. Additionally, we find that mutations in ELG1 suppress the sensitivity of rad5Δ mutants to DNA damage by allowing trans-lesion synthesis to take place. Taken together, the data indicate that the Elg1-RLC complex plays an important role in the maintenance of genomic stability by unloading PCNA from the chromatin.
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