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. 2021 Dec 22;601(7892):268–273. doi: 10.1038/s41586-021-04261-0

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 10 — HR, In HR, following DSB, 5′ DNA ends are resected by nucleases, which generates RPA-coated 3′ overhangs. RPA is displaced by RAD51 giving rise to presynaptic nucleoprotein filament formation. This RAD51-filament invades homologous DNA duplex through its 3′ end. DNA invasion result in D-loop formation, which is extended by DNA synthesis. If the SDSA pathway is invoked, HELQ can disrupt the D-loop to displace and/or anneal the extended strand with the broken duplex via its helicase and strand annealing activities. Alternatively, in DSBR, the D-loop can be greatly extended and RPA-coated DNA strands in D-loop and second 3′ overhang can be captured by HELQ. During this second-end capture step, HELQ strips RPA from ssDNA and anneals complementary DNA strands together to prime DNA synthesis, restoring the broken DNA and resulting in either crossover or non-crossover products. SSA, similar to HR, longer RPA-coated 3′ overhangs can be captured by HELQ. Post capture, HELQ strips RPA from both ssDNAs and actively anneals the DNA strands together using base-pairing. The remaining flaps are cleaved, and nicks are ligated by specific nuclease and ligases completing the DSB repair reaction.