InterPro domain: IPR035901

Nucleases of the GIY-YIG family are involved in many cellular processes, including DNA repair and recombination, transfer of mobile genetic elements, and restriction of incoming foreign DNA. The GIY-YIG superfamily groups together nucleases characterised by the presence of a domain of typically ~100 amino acids, with two short motifs "GIY" and "YIG" in the N-terminal part, followed by an Arg residue in the centre and a Glu residue in the C-terminal part [ 1 , 2 , 3 , 4 , 5 ].

The GIY-YIG domain forms a compact structural domain, which serves as a scaffold for the coordination of a divalent metal ion required for catalysis of the phosphodiester bond cleavage. The GIY-YIG domain has an alpha/bera-sandwich architecture with a central three-stranded antiparallel beta-sheet flanked by three-helices. The three-stranded anti-parallel beta-sheet contains the GIY-YIG sequence elements. The most conserved and putative catalytic residues are located on a shallow, concave surface and include a metal coordination site [ 6 , 6 , 6 , 6 ].

The GIY-YIG domain has been implicated in a variety of cellular processes involving DNA cleavage, from self-propagation with or without introns, to restriction of foreign DNA, to DNA repair and maintenance of genome stability [ 6 ].

Some proteins known to contain a GIY-YIG domain include:

• Eukaryotic Slx-1 proteins, involved in the maintenance of the rDNA copy number. They have a C-terminal RING finger Zn-binding domain.
• Mamalian ankyrin repeat and LEM domain- containing protein 1 (ANKLE1).
• Bacterial and archaeal UvrC subunits of (A)BC excinucleases, which remove damaged nucleotides by incising the damaged strand on both sides of the lesion. Paramecium bursaria Chlorella virus 1 (pbvc1).
• Phage T4 endonucleases SegA to E, probably involved in the movement of the endonuclease-encoding DNA.
• Phage T4 intron-associated endonuclease 1 (I-TevI), specific to the thymidylate synthase (td) gene splice junction and involved in intron homing.

This entry represents GIY-YIG nuclease superfamily, and identifies the GIY-YIG domain in diverse and distantly related superfamily members, such as Slx1 [ 6 ].

1. Configuration of the catalytic GIY-YIG domain of intron endonuclease I-TevI: coincidence of computational and molecular findings. Nucleic Acids Res. 27, 2115-25
2. Catalytic domain structure and hypothesis for function of GIY-YIG intron endonuclease I-TevI. Nat. Struct. Biol. 9, 806-11
3. Structural insights into the first incision reaction during nucleotide excision repair. EMBO J. 24, 885-94
4. Phylogenomic analysis of the GIY-YIG nuclease superfamily. BMC Genomics 7, 98
5. Oligomeric structure diversity within the GIY-YIG nuclease family. J. Mol. Biol. 387, 10-6