ArticleNucleic acids research2016
Overhang polarity of chromosomal double-strand breaks impacts kinetics and fidelity of yeast non-homologous end joining.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Circular single stranded DNA potentiates non-viral gene insertion in hematopoietic stem and progenitor cells.Nature communications · 2025Article
- Yeast EndoG prevents genome instability by degrading extranuclear DNA species.Nature communications · 2024Article
- Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing.Nature communications · 2024Article
- TREX2 enables efficient genome disruption mediated by paired CRISPR-Cas9 nickases that generate 3'-overhanging ends.Molecular therapy. Nucleic acids · 2023Article
- Genetic control of the error-prone repair of a chromosomal double-strand break with 5' overhangs in yeast.Genetics · 2023Article
- Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery.Nature cell biology · 2023Article
- Multidimensional characterization of inducible promoters and a highly light-sensitive LOV-transcription factor.Nature communications · 2023Article
- Genetic control of the error-prone repair of a chromosomal double-strand break with 5' overhangs in yeast.bioRxiv : the preprint server for biology · 2023Article
- Altered DNA repair pathway engagement by engineered CRISPR-Cas9 nucleases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The optimal strategy balancing risk and speed predicts DNA damage checkpoint override times.Nature physics · 2022Article
- Cas9-induced large deletions and small indels are controlled in a convergent fashion.Nature communications · 2022Article
- Mutagenic repair of a ZFN-induced double-strand break in yeast: Effects of cleavage site sequence and spacer size.DNA repair · 2021Article
- Massively parallel kinetic profiling of natural and engineered CRISPR nucleases.Nature biotechnology · 2021Article
- Recombinational Repair of Nuclease-Generated Mitotic Double-Strand Breaks with Different End Structures in Yeast.G3 (Bethesda, Md.) · 2020Article
- Frequency of DNA end joiningProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Ku DNA End-Binding Activity Promotes Repair Fidelity and Influences End-Processing During Nonhomologous End-Joining inGenetics · 2018Article
- Double-stranded DNA break polarity skews repair pathway choice during intrachromosomal and interchromosomal recombination.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- High-Throughput Analysis of DNA Break-Induced Chromosome Rearrangements by Amplicon Sequencing.Methods in enzymology · 2018Article
- Rapidly inducible Cas9 and DSB-ddPCR to probe editing kinetics.Nature methods · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Non-homologous end joining (NHEJ) is the main repair pathway for DNA double-strand breaks (DSBs) in cells with limited 5' resection. To better understand how overhang polarity of chromosomal DSBs affects NHEJ, we made site-specific 5'-overhanging DSBs (5' DSBs) in yeast using an optimized zinc finger nuclease at an efficiency that approached HO-induced 3' DSB formation. When controlled for the extent of DSB formation, repair monitoring suggested that chromosomal 5' DSBs were rejoined more efficiently than 3' DSBs, consistent with a robust recruitment of NHEJ proteins to 5' DSBs. Ligation-mediated qPCR revealed that Mre11-Rad50-Xrs2 rapidly modified 5' DSBs and facilitated protection of 3' DSBs, likely through recognition of overhang polarity by the Mre11 nuclease. Next-generation sequencing revealed that NHEJ at 5' DSBs had a higher mutation frequency, and validated the differential requirement of Pol4 polymerase at 3' and 5' DSBs. The end processing enzyme Tdp1 did not impact joining fidelity at chromosomal 5' DSBs as in previous plasmid studies, although Tdp1 was recruited to only 5' DSBs in a Ku-independent manner. These results suggest distinct DSB handling based on overhang polarity that impacts NHEJ kinetics and fidelity through differential recruitment and action of DSB modifying enzymes.
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Registered trials
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