A fusion protein comprising a zinc finger DNA-binding domain and a polypeptide comprising an engineered wild-type Fok I cleavage half-domain, wherein the engineered cleavage half-domain comprises a mutation selected from the group consisting of: i) substitution mutations in amino acid residues 486, 499 and 496 wherein the wild-type Gln residue at Position 486 is replaced with a Glu residue, the wild-type lie residue at Position 499 is replaced with a Leu or Ala residue and the wild-type Asn residue at Position 496 is replaced with an Asp or Glu residue; ii) substitution mutations in amino acid residues 487 and 496 wherein the wild-type Arg residue at Position 487 is replaced with an Asp residue and the wild-type Asn residue at Position 496 is replaced with an Asp or Glu residue; iii) substitution mutations in amino acid residues 487, 499 and 496 wherein the wild-type Arg residue at position 487 is replaced with an Asp residue, the wild-type lie residue at position 499 is replaced with a Leu or Ala residue and the wild-type Asn residue at position 496 is replaced with an Asp or Glu residue; iv) substitution mutations in amino acid residues 483 and 537 wherein the wild-type Asp residue at position 483 is replaced with an Arg residue and the wild-type His residue at position 537 is replaced with a Lys or Arg residue; v) substitution mutations in amino acid residues 490 and 537 wherein the wild-type Glu residue at position 490 is replaced with a Lys residue and the wild-type His residue at position 537 is replaced with a Lys or Arg residue; vi) substitution mutations in amino acid residues 490, 537 and 538 wherein the wild-type Glu residue at position 490 is replaced with a Lys residue, the wild-type His residue at position 537 is replaced with a Lys or Arg residue and the wild-type lie residue at position 538 is replaced with a Lys or Val residue and vii) substitution mutations in amino acid residues 483, 538 and 537 wherein the wild-type Asp residue at position 483 is replaced with an Arg residue, the wild-type His residue at Position 537 is replaced with a Lys or Arg residue and the wild-type lie residue at position 538 is replaced with a Lys or Val residue, wherein the amino acid residues are numbered relative to the wild-type Fok I. i) substitution mutations in amino acid residues 486, 499 and 496 wherein the wild-type Gln residue at Position 486 is replaced with a Glu residue, the wild-type lie residue at Position 499 is replaced with a Leu or Ala residue and the wild-type Asn residue at Position 496 is replaced with an Asp or Glu residue; ii) substitution mutations in amino acid residues 487 and 496 wherein the wild-type Arg residue at Position 487 is replaced with an Asp residue and the wild-type Asn residue at Position 496 is replaced with an Asp or Glu residue; iii) substitution mutations in amino acid residues 487, 499 and 496 wherein the wild-type Arg residue at position 487 is replaced with an Asp residue, the wild-type lie residue at position 499 is replaced with a Leu or Ala residue and the wild-type Asn residue at position 496 is replaced with an Asp or Glu residue; iv) substitution mutations in amino acid residues 483 and 537 wherein the wild-type Asp residue at position 483 is replaced with an Arg residue and the wild-type His residue at position 537 is replaced with a Lys or Arg residue; v) substitution mutations in amino acid residues 490 and 537 wherein the wild-type Glu residue at position 490 is replaced with a Lys residue and the wild-type His residue at position 537 is replaced with a Lys or Arg residue; vi) substitution mutations in amino acid residues 490, 537 and 538 wherein the wild-type Glu residue at position 490 is replaced with a Lys residue, the wild-type His residue at position 537 is replaced with a Lys or Arg residue and the wild-type lie residue at position 538 is replaced with a Lys or Val residue and vii) substitution mutations in amino acid residues 483, 538 and 537 wherein the wild-type Asp residue at position 483 is replaced with an Arg residue, the wild-type His residue at Position 537 is replaced with a Lys or Arg residue and the wild-type lie residue at position 538 is replaced with a Lys or Val residue,