Distinct functions of human RECQ helicases WRN and BLM in replication fork recovery and progression after hydroxyurea-induced stalling

DNA Repair (Amst). 2013 Feb 1;12(2):128-39. doi: 10.1016/j.dnarep.2012.11.005. Epub 2012 Dec 17.


Human WRN and BLM genes are members of the conserved RECQ helicase family. Mutations in these genes are associated with Werner and Bloom syndromes. WRN and BLM proteins are implicated in DNA replication, recombination, repair, telomere maintenance, and transcription. Using microfluidics-assisted display of DNA for replication track analysis (ma-RTA), we show that WRN and BLM contribute additively to normal replication fork progression, and non-additively, in a RAD51-dependent pathway, to resumption of replication after arrest by hydroxyurea (HU), a replication-stalling drug. WRN but not BLM is required to support fork progression after HU. Resumption of replication by forks may be necessary but is not sufficient for timely completion of the cell cycle after HU arrest, as depletion of WRN or BLM compromises fork recovery to a similar degree, but only BLM depletion leads to extensive delay of cell division after HU, as well as more pronounced chromatin bridging. Finally, we show that recovery from HU includes apparent removal of some of the DNA that was synthesized immediately after release from HU, a novel phenomenon that we refer to as nascent strand processing, NSP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle / drug effects
  • Cell Line
  • Chromatin / drug effects
  • DNA Replication / drug effects
  • DNA Replication / genetics*
  • Exodeoxyribonucleases / metabolism*
  • Humans
  • Hydroxyurea / toxicity
  • Microfluidics
  • Rad51 Recombinase / metabolism
  • RecQ Helicases / metabolism*
  • Werner Syndrome Helicase


  • Chromatin
  • RAD51 protein, human
  • Rad51 Recombinase
  • Exodeoxyribonucleases
  • Bloom syndrome protein
  • RecQ Helicases
  • WRN protein, human
  • Werner Syndrome Helicase
  • Hydroxyurea