ArticleProceedings of the National Academy of Sciences of the United States of America2015
DNA polymerases δ and λ cooperate in repairing double-strand breaks by microhomology-mediated end-joining in Saccharomyces cerevisiae.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 47 citations in OpenAlex.
- Optimizing microhomology-based genome editing by engineering DNA polymerase θ for improved efficiency and reduced on-target indels.Cell reports methods · 2026Article
- Real-Time Visualization of G2L4 Reverse Transcriptase in DNA Repair via Microhomology-Mediated End Joining.bioRxiv : the preprint server for biology · 2026Article
- Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- The CST complex mediates a post-resection non-homologous end joining repair pathway and promotes local deletions in Saccharomyces cerevisiae.Cell genomics · 2025Article
- Eukaryotic Lagging Strand Synthesis is Distributive.bioRxiv : the preprint server for biology · 2025Article
- Recent applications, future perspectives, and limitations of the CRISPR-Cas system.Molecular therapy. Nucleic acids · 2025Review
- Recombination-coupled DNA synthesis facilitates post-invasion steps in meiotic crossover and noncrossover formations.Nucleic acids research · 2025Article
- RPA and Rad27 limit templated and inverted insertions at DNA breaks.Nucleic acids research · 2025Article
- Mechanisms of tandem duplication in the cancer genome.DNA repair · 2025Review
- Microhomology-Mediated End-Joining Chronicles: Tracing the Evolutionary Footprints of Genome Protection.Annual review of cell and developmental biology · 2024Review
- Gross Chromosomal Rearrangement at Centromeres.Biomolecules · 2023Review
- Double-strand breaks induce inverted duplication chromosome rearrangements by a DNA polymerase δ-dependent mechanism.Nature communications · 2023Article
- Article
- Saccharomyces cerevisiae DNA polymerase IV overcomes Rad51 inhibition of DNA polymerase δ in Rad52-mediated direct-repeat recombination.Nucleic acids research · 2023Article
- Multifaceted Nature of DNA Polymerase θ.International journal of molecular sciences · 2023Review
- RNA-guided DNA base damage repair via DNA polymerase-mediated nick translation.Nucleic acids research · 2023Article
- CRISPR-Cas12a induced DNA double-strand breaks are repaired by multiple pathways with different mutation profiles in Magnaporthe oryzae.Nature communications · 2022Article
- A rapid multiplex cell-free assay on biochip to evaluate functional aspects of double-strand break repair.Scientific reports · 2022Article
- The contribution of DNA repair pathways to genome editing and evolution in filamentous pathogens.FEMS microbiology reviews · 2022Review
- Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.Nature communications · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Maintenance of genome stability is carried out by a suite of DNA repair pathways that ensure the repair of damaged DNA and faithful replication of the genome. Of particular importance are the repair pathways, which respond to DNA double-strand breaks (DSBs), and how the efficiency of repair is influenced by sequence homology. In this study, we developed a genetic assay in diploid Saccharomyces cerevisiae cells to analyze DSBs requiring microhomologies for repair, known as microhomology-mediated end-joining (MMEJ). MMEJ repair efficiency increased concomitant with microhomology length and decreased upon introduction of mismatches. The central proteins in homologous recombination (HR), Rad52 and Rad51, suppressed MMEJ in this system, suggesting a competition between HR and MMEJ for the repair of a DSB. Importantly, we found that DNA polymerase delta (Pol δ) is critical for MMEJ, independent of microhomology length and base-pairing continuity. MMEJ recombinants showed evidence that Pol δ proofreading function is active during MMEJ-mediated DSB repair. Furthermore, mutations in Pol δ and DNA polymerase 4 (Pol λ), the DNA polymerase previously implicated in MMEJ, cause a synergistic decrease in MMEJ repair. Pol λ showed faster kinetics associating with MMEJ substrates following DSB induction than Pol δ. The association of Pol δ depended on RAD1, which encodes the flap endonuclease needed to cleave MMEJ intermediates before DNA synthesis. Moreover, Pol δ recruitment was diminished in cells lacking Pol λ. These data suggest cooperative involvement of both polymerases in MMEJ.
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