RESUMO
To cleave DNA, the Type III RM (restriction-modification) enzymes must communicate the relative orientation of two recognition sequences, which may be separated by many thousands of base pairs. This long-range interaction requires ATP hydrolysis by a helicase domain, and both active (DNA translocation) and passive (DNA sliding) modes of motion along DNA have been proposed. Potential roles for ATP binding and hydrolysis by the helicase domains are discussed, with a focus on bipartite ATPases that act as molecular switches.
Assuntos
Trifosfato de Adenosina/farmacologia , DNA/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo III/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo III/fisiologia , Movimento/fisiologia , Animais , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/genética , DNA/química , Humanos , Modelos Biológicos , Conformação de Ácido Nucleico/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Transporte Proteico , Especificidade por SubstratoRESUMO
Many biological processes rely on the interaction of proteins with multiple DNA sites separated by thousands of base pairs. These long-range communication events can be driven by both the thermal motions of proteins and DNA, and directional protein motions that are rectified by ATP hydrolysis. The present review describes conflicting experiments that have sought to explain how the ATP-dependent Type III restriction-modification enzymes can cut DNA with two sites in an inverted repeat, but not DNA with two sites in direct repeat. We suggest that an ATPase activity may not automatically indicate a DNA translocase, but can alternatively indicate a molecular switch that triggers communication by thermally driven DNA sliding. The generality of this mechanism to other ATP-dependent communication processes such as mismatch repair is also discussed.