Catalytic GIY-YIG domain of yeast structure-specific endonuclease subunit SLX1 and its eukaryotic homologs
Structure-specific endonuclease subunit SLX1 is a highly conserved protein from yeast to human, with an N-terminal GIY-YIG endonuclease domain and a C-terminal PHD-type zinc finger postulated to mediate protein-protein or protein-DNA interaction. SLX1 forms active heterodimeric complexes with its SLX4 partner, which has additional roles in the DNA damage response that are distinct from the function of the heterodimeric SLX1-SLX4 nuclease. In yeast, the SLX1-SLX4 complex functions as a 5' flap endonuclease that maintains ribosomal DNA copy number, where SLX1 and SLX4 are shown to be catalytic and regulatory subunits, respectively. This endonuclease introduces single-strand cuts in duplex DNA on the 3' side of junctions with single-strand DNA. In addition to 5' flap endonuclease activity, human SLX1-SLX4 complex has been identified as a Holliday junction resolvase that promotes symmetrical cleavage of static and migrating Holliday junctions. SLX1 also associates with MUS81, EME1, C20orf94, PLK1, and ERCC1. Some eukaryotic SLX1 homologs lack the zinc finger domain, but possess intrinsically unstructured extensions of unknown function. These unstructured segments might be involved in interactions with other proteins.
Comment:Based on similarity to the sequence of Enterobacteria phage T4 homing endonuclease I-Tevi (1LN0).
Comment:The last conserved motif (invariant Asn residue) of GIY-YIG homing endonuclease I-TevI (1LN0) is completely absent in the SLX-1 family members.
Jiyao W et al.(2023). "The conserved domain database in 2023.",