The intrinsically disordered amino-terminal region of human RecQL4: multiple DNA-binding domains confer annealing, strand exchange and G4 DNA binding

Nucleic Acids Res. 2014 Nov 10;42(20):12614-27. doi: 10.1093/nar/gku993. Epub 2014 Oct 21.


Human RecQL4 belongs to the ubiquitous RecQ helicase family. Its N-terminal region represents the only homologue of the essential DNA replication initiation factor Sld2 of Saccharomyces cerevisiae, and also participates in the vertebrate initiation of DNA replication. Here, we utilized a random screen to identify N-terminal fragments of human RecQL4 that could be stably expressed in and purified from Escherichia coli. Biophysical characterization of these fragments revealed that the Sld2 homologous RecQL4 N-terminal domain carries large intrinsically disordered regions. The N-terminal fragments were sufficient for the strong annealing activity of RecQL4. Moreover, this activity appeared to be the basis for an ATP-independent strand exchange activity. Both activities relied on multiple DNA-binding sites with affinities to single-stranded, double-stranded and Y-structured DNA. Finally, we found a remarkable affinity of the N-terminus for guanine quadruplex (G4) DNA, exceeding the affinities for other DNA structures by at least 60-fold. Together, these findings suggest that the DNA interactions mediated by the N-terminal region of human RecQL4 represent a central function at the replication fork. The presented data may also provide a mechanistic explanation for the role of elements with a G4-forming propensity identified in the vicinity of vertebrate origins of DNA replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA / chemistry
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry
  • G-Quadruplexes
  • Humans
  • Intrinsically Disordered Proteins / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • RecQ Helicases / chemistry*
  • RecQ Helicases / metabolism*


  • DNA-Binding Proteins
  • Intrinsically Disordered Proteins
  • DNA
  • RECQL4 protein, human
  • RecQ Helicases