Strand asymmetry influences mismatch resolution during single-strand annealing
Pokusaeva V, Diez AR, Espinar L, Pérez AT, Filion GJ. 2022. Strand asymmetry influences mismatch resolution during single-strand annealing. Genome Biology. 23, 93.
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Author
Pokusaeva, VictoriaISTA ;
Diez, Aránzazu Rosado;
Espinar, Lorena;
Pérez, Albert Torelló;
Filion, Guillaume J.
Department
Abstract
Background: Biases of DNA repair can shape the nucleotide landscape of genomes at evolutionary timescales. The molecular mechanisms of those biases are still poorly understood because it is difficult to isolate the contributions of DNA repair from those of DNA damage.
Results: Here, we develop a genome-wide assay whereby the same DNA lesion is repaired in different genomic contexts. We insert thousands of barcoded transposons carrying a reporter of DNA mismatch repair in the genome of mouse embryonic stem cells. Upon inducing a double-strand break between tandem repeats, a mismatch is generated if the break is repaired through single-strand annealing. The resolution of the mismatch showed a 60–80% bias in favor of the strand with the longest 3′ flap. The location of the lesion in the genome and the type of mismatch had little influence on the bias. Instead, we observe a complete reversal of the bias when the longest 3′ flap is moved to the opposite strand by changing the position of the double-strand break in the reporter.
Conclusions: These results suggest that the processing of the double-strand break has a major influence on the repair of mismatches during single-strand annealing.
Publishing Year
Date Published
2022-04-12
Journal Title
Genome Biology
Acknowledgement
We acknowledge the financial support of the Natural Sciences and Engineering Research Council of Canada (NSERC RGPIN-2020-06377), the Spanish Ministry of Economy, Industry and Competitiveness (“Centro de Excelencia Severo Ochoa 2013-2017”, Plan Estatal PGC2018-099807-B-I00), of the CERCA Programme/Generalitat de Catalunya, and of the European Research Council (Synergy Grant 609989). VOP was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie programme (665385). We also acknowledge the support of the Spanish Ministry of Economy and Competitiveness (MEIC) to the EMBL partnership.
Volume
23
Article Number
93
ISSN
IST-REx-ID
Cite this
Pokusaeva V, Diez AR, Espinar L, Pérez AT, Filion GJ. Strand asymmetry influences mismatch resolution during single-strand annealing. Genome Biology. 2022;23. doi:10.1186/s13059-022-02665-3
Pokusaeva, V., Diez, A. R., Espinar, L., Pérez, A. T., & Filion, G. J. (2022). Strand asymmetry influences mismatch resolution during single-strand annealing. Genome Biology. Springer Nature. https://doi.org/10.1186/s13059-022-02665-3
Pokusaeva, Victoria, Aránzazu Rosado Diez, Lorena Espinar, Albert Torelló Pérez, and Guillaume J. Filion. “Strand Asymmetry Influences Mismatch Resolution during Single-Strand Annealing.” Genome Biology. Springer Nature, 2022. https://doi.org/10.1186/s13059-022-02665-3.
V. Pokusaeva, A. R. Diez, L. Espinar, A. T. Pérez, and G. J. Filion, “Strand asymmetry influences mismatch resolution during single-strand annealing,” Genome Biology, vol. 23. Springer Nature, 2022.
Pokusaeva V, Diez AR, Espinar L, Pérez AT, Filion GJ. 2022. Strand asymmetry influences mismatch resolution during single-strand annealing. Genome Biology. 23, 93.
Pokusaeva, Victoria, et al. “Strand Asymmetry Influences Mismatch Resolution during Single-Strand Annealing.” Genome Biology, vol. 23, 93, Springer Nature, 2022, doi:10.1186/s13059-022-02665-3.
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