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Direct Involvement of Retinoblastoma Family Proteins in DNA Repair by Non-homologous End-Joining.

Cook, R; Zoumpoulidou, G; Luczynski, MT; Rieger, S; Moquet, J; Spanswick, VJ; Hartley, JA; ... Mittnacht, S; + view all (2015) Direct Involvement of Retinoblastoma Family Proteins in DNA Repair by Non-homologous End-Joining. Cell Rep , 10 (12) 2006 - 2018. 10.1016/j.celrep.2015.02.059. Green open access

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Abstract

Deficiencies in DNA double-strand break (DSB) repair lead to genetic instability, a recognized cause of cancer initiation and evolution. We report that the retinoblastoma tumor suppressor protein (RB1) is required for DNA DSB repair by canonical non-homologous end-joining (cNHEJ). Support of cNHEJ involves a mechanism independent of RB1's cell-cycle function and depends on its amino terminal domain with which it binds to NHEJ components XRCC5 and XRCC6. Cells with engineered loss of RB family function as well as cancer-derived cells with mutational RB1 loss show substantially reduced levels of cNHEJ. RB1 variants disabled for the interaction with XRCC5 and XRCC6, including a cancer-associated variant, are unable to support cNHEJ despite being able to confer cell-cycle control. Our data identify RB1 loss as a candidate driver of structural genomic instability and a causative factor for cancer somatic heterogeneity and evolution.

Type: Article
Title: Direct Involvement of Retinoblastoma Family Proteins in DNA Repair by Non-homologous End-Joining.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2015.02.059
Publisher version: http://dx.doi.org/10.1016/j.celrep.2015.02.059
Language: English
Additional information: © 2015 The Authors This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/1464976
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