Transcription and mRNA export machineries SAGA and TREX-2 maintain monoubiquitinated H2B balance required for DNA repair
| Autor: | Federica M. Evangelista, Matthieu Stierle, Anne Maglott-Roth, Laszlo Tora, Laurent Brino, Evi Soutoglou |
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| Přispěvatelé: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genome instability Transcription Genetic DNA repair Protein subunit [SDV]Life Sciences [q-bio] Biological Transport Active Biology Article Histones 03 medical and health sciences Transcription (biology) Acetyltransferases Coactivator Histone H2B Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger Research Articles ComputingMilieux_MISCELLANEOUS Intracellular Signaling Peptides and Proteins Ubiquitination Recombinational DNA Repair Cell Biology Phosphoproteins Cell biology 030104 developmental biology Histone Exodeoxyribonucleases biology.protein Trans-Activators Homologous recombination HeLa Cells Transcription Factors |
| Zdroj: | Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, 2018, 217 (10), pp.3382-3397. ⟨10.1083/jcb.201803074⟩ The Journal of Cell Biology |
| ISSN: | 0021-9525 1540-8140 |
| Popis: | The SAGA coactivator complex and the nuclear pore–associated TREX-2 complex couple transcription with mRNA export. Evangelista et al. identify a novel interplay between TREX-2 and the deubiquitination module of SAGA that is necessary to maintain monoubiquitinated H2B levels required for efficient DNA repair through homologous recombination. DNA repair is critical to maintaining genome integrity, and its dysfunction can cause accumulation of unresolved damage that leads to genomic instability. The Spt–Ada–Gcn5 acetyltransferase (SAGA) coactivator complex and the nuclear pore–associated transcription and export complex 2 (TREX-2) couple transcription with mRNA export. In this study, we identify a novel interplay between human TREX-2 and the deubiquitination module (DUBm) of SAGA required for genome stability. We find that the scaffold subunit of TREX-2, GANP, positively regulates DNA repair through homologous recombination (HR). In contrast, DUBm adaptor subunits ENY2 and ATXNL3 are required to limit unscheduled HR. These opposite roles are achieved through monoubiquitinated histone H2B (H2Bub1). Interestingly, the activity of the DUBm of SAGA on H2Bub1 is dependent on the integrity of the TREX-2 complex. Thus, we describe the existence of a functional interaction between human TREX-2 and SAGA DUBm that is key to maintaining the H2B/HB2ub1 balance needed for efficient repair and HR. |
| Databáze: | OpenAIRE |
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