2026-04-27T03:34:11Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/274422026-04-25T00:18:13Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
de Alba, Ernesto López
author
Salguero, Israel
author
Giménez-Llorente, Daniel
author
Montes-Torres, Javier
author
Fernández-Sanromán, Ángel
author
Casajús-Pelegay, Ester
author
Terrón-Bautista, José
author
Barroso-González, Jonathan
author
Bernal, Juan A
author
Macintyre, Geoff
author
Fernández-Leiro, Rafael
author
Losada, Ana
author
Cortés-Ledesma, Felipe
2026-04-24T12:31:39Z
2026-04-24T12:31:39Z
2025-10-02
Science. 2025 Oct 2;390(6768):eadr5048.
https://hdl.handle.net/20.500.12105/27442
41037600
Science
The analysis of DNA sequence outcomes provides molecular insights into double-strand break (DSB) repair mechanisms. Using parallel in-pool profiling of Cas9-induced insertions and deletions (indels) within a genome-wide knockout library, we present a comprehensive catalog that assesses the influence of nearly every human gene on DSB repair outcomes. This REPAIRome resource uncovers uncharacterized mechanisms, pathways, and factors involved in DSB repair, including opposing roles for XLF and PAXX, a molecular explanation for Cas9-induced multinucleotide insertions, HLTF functions in Cas9-induced DSB repair, the involvement of the SAGA complex in microhomology-mediated end joining, and an indel mutational signature linked to VHL loss, renal carcinoma, and hypoxia. These results exemplify the potential of REPAIRome to drive future discoveries in DSB repair, CRISPR-Cas gene editing and the etiology of cancer mutational signatures.
eng
A comprehensive genetic catalog of human double-strand break repair.
research article
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URL
https://repisalud.isciii.es/bitstreams/127997a8-5062-4cff-baa2-4b9c226aad82/download
File
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e0cc4c981a3384868155c46f145df759
190917
application/pdf
A comprehensive genetic catalog of human_Science_2025.pdf