Budding yeast Slx4 interacts with the structure-specific endonuclease Slx1 to ensure completion of ribosomal DNA replication. Slx4 also interacts with the Rad1-Rad10 endonuclease to control cleavage of 3′ flaps during repair of double-strand breaks (DSBs). Here we describe the identification of human SLX4, a scaffold for DNA repair nucleases XPF-ERCC1, MUS81-EME1, and SLX1. SLX4 immunoprecipitates show SLX1-dependent nuclease activity toward Holliday junctions and MUS81-dependent activity toward other branched DNA structures. Furthermore, SLX4 enhances the nuclease activity of SLX1, MUS81, and XPF. Consistent with a role in processing recombination intermediates, cells depleted of SLX4 are hypersensitive to genotoxins that cause DSBs and show defects in the resolution of interstrand crosslink-induced DSBs. Depletion of SLX4 causes a decrease in DSB-induced homologous recombination. These data show that SLX4 is a regulator of structure-specific nucleases and that SLX4 and SLX1 are important regulators of genome stability in human cells.

DNA
dx.doi.org/10.1016/j.molcel.2009.06.020, hdl.handle.net/1765/24472
Molecular Cell
Erasmus MC: University Medical Center Rotterdam

Muñoz, I.M, Hain, K, Déclais, A.C, Gardiner, M, Toh, G.W, Sanchez-Pulido, L, … Rouse, J. (2009). Coordination of Structure-Specific Nucleases by Human SLX4/BTBD12 Is Required for DNA Repair. Molecular Cell, 35(1), 116–127. doi:10.1016/j.molcel.2009.06.020