title: Structure and mechanism of nucleases regulated by SLX4.
abstract: SLX4 is a multidomain platform that regulates various proteins that are involved in genome maintenance and stability. Among these proteins are three structure-selective nucleases (SSEs). XPF-ERCC1 and MUS81-EME1 are structurally similar and function as heterodimers of highly similar subunits, in which only one is active. Two independent modules are formed from subunits of the heterodimers - a dimer of nuclease and nuclease-like domains and a dimer of tandem helix-hairpin-helix HhH2 domains. Both modules are responsible for substrate recognition. The third SSE, SLX1, contains GIY-YIG and RING domains and is a promiscuous nuclease. Structural data imply that SLX1 exists in free form as an autoinhibited homodimer. Association with SLX4 platform disrupts the homodimer and activates SLX1. This review discusses the available structural and mechanistic information on SLX4-regulated SSEs.
authors.affiliation: Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Warsaw, Poland. Electronic address: mnowotny@iimcb.gov.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Nowotny
authors.affiliation: Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Warsaw, Poland. Electronic address: vgaur@iimcb.gov.pl.
authors.forename: Vineet
authors.initials: V
authors.lastname: Gaur
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004720:Endonucleases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D005810:Multigene Family; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D045522:Recombinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D045522:Recombinases; D004247:DNA; D004720:Endonucleases