Evangelista, Federica M, Maglott-Roth, Anne, Stierle, Matthieu, Brino, Laurent, Soutoglou, Evi and Tora, Laszlo (2018) Transcription and mRNA export machineries SAGA and TREX-2 maintain monoubiquitinated H2B balance required for DNA repair. Journal of Cell Biology, 217 (10). pp. 3382-3397. ISSN 0021-9525

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Abstract

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.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor:	Mx Elements Account
Depositing User:	Mx Elements Account
Date Deposited:	13 Jul 2020 07:02
Last Modified:	13 Jul 2020 07:15
URI:	http://sro.sussex.ac.uk/id/eprint/92499

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