Structural Insights of the DciA Helicase Loader in Its Relationship with DNA

Int J Mol Sci. 2023 Jan 11;24(2):1427. doi: 10.3390/ijms24021427.

Abstract

DciA is the ancestral bacterial replicative helicase loader, punctually replaced during evolution by the DnaC/I loaders of phage origin. DnaC helps the helicase to load onto DNA by cracking open the hexameric ring, but the mechanism of loading by DciA remains unknown. We demonstrate by electron microscopy, nuclear magnetic resonance (NMR) spectroscopy, and biochemistry experiments that DciA, which folds into a KH-like domain, interacts with not only single-stranded but also double-stranded DNA, in an atypical mode. Some point mutations of the long α-helix 1 demonstrate its importance in the interaction of DciA for various DNA substrates mimicking single-stranded, double-stranded, and forked DNA. Some of these mutations also affect the loading of the helicase by DciA. We come to the hypothesis that DciA could be a DNA chaperone by intercalating itself between the two DNA strands to stabilize it. This work allows us to propose that the direct interaction of DciA with DNA could play a role in the loading mechanism of the helicase.

Keywords: DNA interaction; DciA; replicative helicase loading; structural study.

MeSH terms

  • Bacteria / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • DNA
  • DNA Helicases / metabolism
  • DNA Replication
  • DNA, Single-Stranded
  • Escherichia coli Proteins* / chemistry
  • Escherichia coli Proteins* / genetics

Substances

  • Escherichia coli Proteins
  • DNA Helicases
  • DNA
  • DNA, Single-Stranded
  • Bacterial Proteins