ArticleProceedings of the National Academy of Sciences of the United States of America2013
Putative antirecombinase Srs2 DNA helicase promotes noncrossover homologous recombination avoiding loss of heterozygosity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- The precision strategy of human genome correction via a set of circular donor DNA and its cleaver.Frontiers in genome editing · 2026Article
- The separation pin distinguishes the pro- and anti-recombinogenic functions of Saccharomyces cerevisiae Srs2.Nature communications · 2023Article
- Delineation of two multi-invasion-induced rearrangement pathways that differently affect genome stability.Genes & development · 2023Article
- Delineation of two multi-invasion-induced rearrangement pathways that differently affect genome stability.bioRxiv : the preprint server for biology · 2023Article
- Review
- Intricate SUMO-based control of the homologous recombination machinery.Genes & development · 2019Review
- Article
- SUMOylation of PCNA by PIAS1 and PIAS4 promotes template switch in the chicken and human B cell lines.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Nonfilament-forming RecA dimer catalyzes homologous joint formation.Nucleic acids research · 2018Article
- Article
- Flap endonuclease overexpression drives genome instability and DNA damage hypersensitivity in a PCNA-dependent manner.Nucleic acids research · 2018Article
- Tight Regulation of Srs2 Helicase Activity Is Crucial for Proper Functioning of DNA Repair Mechanisms.G3 (Bethesda, Md.) · 2018Article
- Putting together and taking apart: assembly and disassembly of the Rad51 nucleoprotein filament in DNA repair and genome stability.Cell stress · 2018Review
- Srs2 promotes synthesis-dependent strand annealing by disrupting DNA polymerase δ-extending D-loops.eLife · 2017Article
- Article
- Genome maintenance in Saccharomyces cerevisiae: the role of SUMO and SUMO-targeted ubiquitin ligases.Nucleic acids research · 2017Review
- Multifunctional roles of Saccharomyces cerevisiae Srs2 protein in replication, recombination and repair.FEMS yeast research · 2017Review
- Rad51 and RecA juxtapose dsDNA ends ready for DNA ligase-catalyzed end-joining under recombinase-suppressive conditions.Nucleic acids research · 2017Article
- Srs2 and Mus81-Mms4 Prevent Accumulation of Toxic Inter-Homolog Recombination Intermediates.PLoS genetics · 2016Article
- Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage alone or DNA replication fork arrest at damaged sites may induce DNA double-strand breaks and initiate homologous recombination. This event can result in a crossover with a homologous chromosome, causing loss of heterozygosity along the chromosome. It is known that Srs2 acts as an antirecombinase at the replication fork: it is recruited by the SUMO (a small ubiquitin-related modifier)-conjugated DNA-polymerase sliding clamp (PCNA) and interferes with Rad51/Rad52-mediated homologous recombination. Here, we report that Srs2 promotes another type of homologous recombination that produces noncrossover products only, in collaboration with PCNA and Rad51. Srs2 proteins lacking the Rad51-binding domain, PCNA-SUMO-binding motifs, or ATP hydrolysis-dependent DNA helicase activity reduce this noncrossover recombination. However, the removal of either the Rad51-binding domain or the PCNA-binding motif strongly increases crossovers. Srs2 gene mutations are epistatic to mutations in the PCNA modification-related genes encoding PCNA, Siz1 (a SUMO ligase) and Rad6 (a ubiquitin-conjugating protein). Knocking out RAD51 blocked this recombination but enhanced nonhomologous end-joining. We hypothesize that, during DNA double-strand break repair, Srs2 mediates collaboration between the Rad51 nucleofilament and PCNA-SUMO and directs the heteroduplex intermediate to DNA synthesis in a moving bubble. This Rad51/Rad52/Srs2/PCNA-mediated noncrossover pathway avoids both interchromosomal crossover and imprecise end-joining, two potential paths leading to loss of heterozygosity, and contributes to genome maintenance and human health.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.