Conferring substrate specificity to DNA helicases: role of the RecQ HRDC domain

Structure. 2005 Aug;13(8):1173-82. doi: 10.1016/j.str.2005.04.018.


RecQ DNA helicases are multidomain enzymes that play pivotal roles in genome maintenance pathways. While the ATPase and helicase activities of these enzymes can be attributed to the conserved catalytic core domain, the role of the Helicase-and-RNase-D-C-terminal (HRDC) domain in RecQ function has yet to be elucidated. Here, we report the crystal structure of the E. coli RecQ HRDC domain, revealing a globular fold that resembles known DNA binding domains. We show that this domain preferentially binds single-stranded DNA and identify its DNA binding surface. HRDC domain mutations in full-length RecQ lead to surprising differences in its structure-specific DNA binding properties. These data support a model in which naturally occurring variations in DNA binding residues among diverse RecQ homologs serve to target these enzymes to distinct substrates and provide insight into a mechanism whereby RecQ enzymes have evolved distinct functions in organisms that encode multiple recQ genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA, Single-Stranded / metabolism*
  • Escherichia coli / enzymology
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • RecQ Helicases / chemistry
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism*
  • Structural Homology, Protein
  • Substrate Specificity


  • DNA, Single-Stranded
  • RecQ Helicases

Associated data

  • PDB/1WUD