The SLX4 Complex Is a SUMO E3 Ligase that Impacts on Replication Stress Outcome and Genome Stability

Jean-Hugues Guervilly (1) , Arato Takedachi (1) , Valeria L Naim (2) , Sarah Scaglione (1) , Charly Chawhan (3) , Yoann L Lovera (1) , Emmanuelle L Despras (2) , Isao Kuraoka (4) , Patricia L Kannouche (2) , Filippo L Rosselli (2) , Pierre-Henri L Gaillard (1)

1 CRCM - Centre de Recherche en Cancérologie de Marseille
2 UMR 8200 - Stabilité Génétique et Oncogenèse
3 Centre for Genome Damage and Stability
4 Osaka University [Osaka]

The SLX4 Fanconi anemia protein is a tumor suppres- sor that may act as a key regulator that engages the cell into specific genome maintenance pathways. Here, we show that the SLX4 complex is a SUMO E3 ligase that SUMOylates SLX4 itself and the XPF sub- unit of the DNA repair/recombination XPF-ERCC1 endonuclease. This SLX4-dependent activity is medi- ated by a remarkably specific interaction between SLX4 and the SUMO-charged E2 conjugating enzyme UBC9 and relies not only on newly identified SUMO- interacting motifs (SIMs) in SLX4 but also on its BTB domain. In contrast to its ubiquitin-binding UBZ4 motifs, SLX4 SIMs are dispensable for its DNA inter- strand crosslink repair functions. Instead, while detri- mental in response to global replication stress, the SUMO E3 ligase activity of the SLX4 complex is crit- ical to prevent mitotic catastrophe following common fragile site expression.

Domaines: Biochimie, Biologie Moléculaire

Jean-Hugues Guervilly, Arato Takedachi, Valeria L Naim, Sarah Scaglione, Charly Chawhan, et al.. The SLX4 Complex Is a SUMO E3 Ligase that Impacts on Replication Stress Outcome and Genome Stability. Molecular Cell, 2015, 57 (1), pp.123-137. ⟨10.1016/j.molcel.2014.11.014⟩. ⟨hal-01429041⟩