Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair.

Journal article

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.

Authors: Muñoz, I; Hain, K; Déclais, A; Gardiner, M; Toh, G

• Publication status: Published
• Journal: Molecular cell
• Volume: 35
• Issue: 1
• Pages: 116-127
• Publication date: 2009-07-01
• DOI: 10.1016/j.molcel.2009.06.020
• EISSN: 1097-4164
• ISSN: 1097-2765
• Language: English
• Keywords: Protein Binding; Cell Line, Tumor; Blotting, Western; Recombinases; Endonucleases; Green Fluorescent Proteins; DNA Repair; Humans; DNA-Binding Proteins; Two-Hybrid System Techniques; DNA Breaks, Double-Stranded; Transfection; Immunoprecipitation; Cell Line; RNA, Small Interfering