Metabolism of DNA secondary structures at the eukaryotic replication fork

DNA Repair (Amst). 2014 Jul;19:152-62. doi: 10.1016/j.dnarep.2014.03.016. Epub 2014 May 9.


DNA secondary structures are largely advantageous for numerous cellular processes but can pose specific threats to the progression of the replication machinery and therefore genome duplication and cell division. A number of specialized enzymes dismantle these structures to allow replication fork progression to proceed faithfully. In this review, we discuss the in vitro and in vivo data that has lead to the identification of these enzymes in eukaryotes, and the evidence that suggests that they act specifically at replication forks to resolve secondary structures. We focus on the role of helicases, which catalyze the dissociation of nucleotide complexes, and on the role of nucleases, which cleave secondary structures to allow replication fork progression at the expense of local rearrangements. Finally, we discuss outstanding questions in terms of dismantling DNA secondary structures, as well as the interplay between diverse enzymes that act upon specific types of structures.

Keywords: DNA secondary structures; Fork reversal; G-quadruplexes; Hairpins; Helicase; Nuclease; Replication fork; Telomere loops; Trinucleotide repeats.

MeSH terms

  • DNA Damage / genetics
  • DNA Helicases / genetics
  • DNA Repair / genetics*
  • DNA Replication / genetics*
  • Deoxyribonucleases / genetics
  • Deoxyribonucleases / metabolism
  • Eukaryota / genetics*
  • G-Quadruplexes
  • Humans
  • Inverted Repeat Sequences
  • Nucleic Acid Conformation
  • Telomere / genetics*
  • Trinucleotide Repeats / genetics


  • Deoxyribonucleases
  • DNA Helicases