Structures, Mechanisms, and Functions of His-Me Finger Nucleases.

His-Me finger (also called HNH or beta beta alpha-me) nucleases, are a large superfamily of nucleases that share limited sequence homology, but all members carry a highly similar catalytic motif exhibiting a beta beta alpha topology. This review represents a structural comparison of His-Me finger nucleases, summarizing their substrate-binding and recognition strategies, mechanisms of enzymatic hydrolysis, cellular functions, and the various means of activity regulation. His-Me finger nucleases usually function as monomers, making a single nick in nucleic acids to degrade foreign or host genomes, or as homodimers that introduce double-stranded DNA breaks for DNA restriction, integration, recombination, and repair. Various cellular neutralizing machineries have evolved to regulate the activity of His-Me finger nucleases, thereby maintaining genome integrity and cellular functionality.