ArticleNucleic acids research2022
Characterization of sequence contexts that favor alternative end joining at Cas9-induced double-strand breaks.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- DNA polymerase theta (Polθ): a novel candidate for targeted cancer therapy.Cancer biology & therapy · 2026Review
- Indel pattern-guided repair mapping reveals genome-wide DNA repair networks in CRISPR/Cas9 editing.Nucleic acids research · 2026Article
- Features affecting Cas9-induced editing efficiency and patterns in tomato: evidence from a large CRISPR dataset.The Plant journal : for cell and molecular biology · 2026Article
- Microhomology-mediated end joining is the predominant form of DNA repair in the mosquito Aedes aegypti with implications for gene editing, gene drive, and transgene removal.Nucleic acids research · 2026Article
- Strategies to improve the efficiency of homing gene drives with multiplexed gRNAs.BMC biology · 2025Article
- Emerging insights into alternative end‑joining: Mechanisms, genome instability and therapeutic opportunities in cancer (Review).International journal of oncology · 2025Review
- Coordinated transfer of DNA between Pol θ and Pol δ resets microhomology choice during double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Defining APOBEC-induced mutation signatures and modifying activities in yeast.Methods in enzymology · 2025Article
- CRISPR/Cas system and its application in the diagnosis of animal infectious diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Microhomology-Mediated End-Joining Chronicles: Tracing the Evolutionary Footprints of Genome Protection.Annual review of cell and developmental biology · 2024Review
- Dynamic stem-loop extension by Pol θ and templated insertion during DNA repair.The Journal of biological chemistry · 2024Article
- Sequential requirements for distinct Polθ domains during theta-mediated end joining.Molecular cell · 2024Article
- Templated insertions-DNA repair gets acrobatic.Environmental and molecular mutagenesis · 2024Review
- Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1.EMBO molecular medicine · 2024Article
- Balanced Translocation DisruptingHuman mutation · 2023Article
- Polθ Inhibition: An Anticancer Therapy for HR-Deficient Tumours.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alternative end joining (alt-EJ) mechanisms, such as polymerase theta-mediated end joining, are increasingly recognized as important contributors to inaccurate double-strand break repair. We previously proposed an alt-EJ model whereby short DNA repeats near a double-strand break anneal to form secondary structures that prime limited DNA synthesis. The nascent DNA then pairs with microhomologous sequences on the other break end. This synthesis-dependent microhomology-mediated end joining (SD-MMEJ) explains many of the alt-EJ repair products recovered following I-SceI nuclease cutting in Drosophila. However, sequence-specific factors that influence SD-MMEJ repair remain to be fully characterized. Here, we expand the utility of the SD-MMEJ model through computational analysis of repair products at Cas9-induced double-strand breaks for 1100 different sequence contexts. We find evidence at single nucleotide resolution for sequence characteristics that drive successful SD-MMEJ repair. These include optimal primer repeat length, distance of repeats from the break, flexibility of DNA sequence between primer repeats, and positioning of microhomology templates relative to preferred primer repeats. In addition, we show that DNA polymerase theta is necessary for most SD-MMEJ repair at Cas9 breaks. The analysis described here includes a computational pipeline that can be utilized to characterize preferred mechanisms of alt-EJ repair in any sequence context.
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