The Type I and III Restriction Endonucleases: Structural Elements in Molecular Motors that Process DNA

Abstract

The Type I and III restriction endonucleases are large, multimeric protein complexes with four enzyme activities; DNA methyltransferase, DNA endonuclease, ATPase and DNA translocase. It has been demonstrated that ATP-dependent protein motion along DNA is necessary for endonuclease activity. Studies have shown that Type I enzymes remain bound to their recognition sites whilst simultaneously translocating adjacent non-specific dsDNA past a stationary complex. This occurs bi-directionally so that two DNAloops are extruded. An equivalent unidirectional mechanism has been suggested for the Type III enzymes. DNA cleavage generally results when the enzymes stall against another restriction enzyme complex. Both the HsdR subunits of the Type I enzymes and the Res subunits of the Type III enzymes carry amino acid motifs characteristic of superfamily 2 helicases. In this review, the structural and mechanistic implications of this relationship are discussed and models suggested for how the ATP-dependent restriction enzymes might couple chemical energy to mechanical motion on DNA.