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https://doi.org/10.1016/j.molcel.2020.12.006
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Hewitt, Graeme | - |
dc.contributor.author | Borel, Valerie | - |
dc.contributor.author | Segura-Bayona, Sandra | - |
dc.contributor.author | Takaki, Tohru | - |
dc.contributor.author | Ruis, Phil | - |
dc.contributor.author | Bellelli, Roberto | - |
dc.contributor.author | Lehmann, Laura C | - |
dc.contributor.author | Sommerova, Lucia | - |
dc.contributor.author | Vancevska, Aleksandra | - |
dc.contributor.author | Tomas-Loba, Antonia | - |
dc.contributor.author | Zhu, Kang | - |
dc.contributor.author | Cooper, Christopher | - |
dc.contributor.author | Fugger, Kasper | - |
dc.contributor.author | Patel, Harshil | - |
dc.contributor.author | Goldstone, Robert | - |
dc.contributor.author | Schneider-Luftman, Deborah | - |
dc.contributor.author | Herbert, Ellie | - |
dc.contributor.author | Stamp, Gordon | - |
dc.contributor.author | Brough, Rachel | - |
dc.contributor.author | Pettitt, Stephen | - |
dc.contributor.author | Lord, Christopher J | - |
dc.contributor.author | West, Stephen C | - |
dc.contributor.author | Ahel, Ivan | - |
dc.contributor.author | Ahel, Dragana | - |
dc.contributor.author | Chapman, J Ross | - |
dc.contributor.author | Deindl, Sebastian | - |
dc.contributor.author | Boulton, Simon J | - |
dc.contributor.other | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Departamento de Fisiología | - |
dc.date.accessioned | 2024-02-07T08:08:35Z | - |
dc.date.available | 2024-02-07T08:08:35Z | - |
dc.date.issued | 2021-02-18 | - |
dc.identifier.citation | Molecular Cell 81, 767–783, 2021 | es |
dc.identifier.issn | Print: 1097-2765 | - |
dc.identifier.issn | Electrónico: 1097-4164 | - |
dc.identifier.uri | http://hdl.handle.net/10201/138806 | - |
dc.description | ©2020 The Author(s). This document is the Published version of a Published Work that appeared in final form in Molecular Cell. To access the final edited and published work see https://doi.org/10.1016/j.molcel.2020.12.006 | - |
dc.description.abstract | Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair remains unknown. Here we report that loss of ALC1 confers sensitivity to PARP inhibitors, methyl-methanesulfonate, and uracil misincorporation, which reflects the need to remodel nucleosomes following base excision by DNA glycosylases but prior to handover to APEX1. Using CRISPR screens, we establish that ALC1 loss is synthetic lethal with homologous recombination deficiency (HRD), which we attri- bute to chromosome instability caused by unrepaired DNA gaps at replication forks. In the absence of ALC1 or APEX1, incomplete processing of BER intermediates results in post-replicative DNA gaps and a critical dependence on HR for repair. Hence, targeting ALC1 alone or as a PARP inhibitor sensitizer could be em- ployed to augment existing therapeutic strategies for HRD cancers | - |
dc.format | application/pdf | es |
dc.format.extent | 29 | es |
dc.language | eng | es |
dc.publisher | Cell Press | es |
dc.relation | Wellcome Trust (grant number 210634), BBSRC (BB/R007195/1), and Cancer Research UK (C35050/A22284). Cancer Research UK Career Development Fellowship (grant number 16304). Cancer Research UK (FC0010048), the UK Medical Research Council (FC0010048), and the Wellcome Trust (FC0010048); a European Research Council (ERC) Advanced Investigator Grant (TelMetab); and Wellcome Trust Senior Investigator and Collaborative Grants. EMBO Long Term Fellowship (ALTF 707-2019) and a MSCA individual fellowship (grant 886577). CRUK Career Development Fellowship (C52690/A19270), Wellcome core award 090532/Z/09/Z. | es |
dc.rights | info:eu-repo/semantics/embargoedAccess | es |
dc.subject.other | CDU::5 - Ciencias puras y naturales::57 - Ciencias biológicas en general:577 - 577 Bioquímica. Biología molecular. Biofísica | - |
dc.title | Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD | es |
dc.type | info:eu-repo/semantics/article | es |
dc.embargo.terms | Si | - |
dc.identifier.doi | https://doi.org/10.1016/j.molcel.2020.12.006 | - |
Aparece en las colecciones: | Artículos: Fisiología |
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Fichero | Descripción | Tamaño | Formato | |
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ALC1.pdf | 5,45 MB | Adobe PDF | Visualizar/Abrir Solicitar una copia |
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