The catalytic mechanisms of type II restriction endonucleases and homing endonucleases are discussed and compared. Brief reviews of the chemistry of phosphoryl transfers and canonical one-metal and two-metal endonucleolytic mechanisms are provided along with possible future directions in the study of endonuclease active sites. The discussion of type II restriction endonucleases is comprised of a description of the general architecture of the canonical active site structural motif followed by more in-depth examples of one- and two-metal mechanisms. The homing endonuclease section is comprised of four sections describing what is known regarding the cleavage mechanisms of the four group I intron homing endonuclease families: LAGLIDADG, His-Cys box, H-N-H, and GIY-YIG.
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