Roles of ChlR1 DNA helicase in replication recovery from DNA damage

Exp Cell Res. 2013 Aug 15;319(14):2244-53. doi: 10.1016/j.yexcr.2013.06.005. Epub 2013 Jun 22.

Abstract

The ChlR1 DNA helicase is mutated in Warsaw breakage syndrome characterized by developmental anomalies, chromosomal breakage, and sister chromatid cohesion defects. However, the mechanism by which ChlR1 preserves genomic integrity is largely unknown. Here, we describe the roles of ChlR1 in DNA replication recovery. We show that ChlR1 depletion renders human cells highly sensitive to cisplatin; an interstrand-crosslinking agent that causes stalled replication forks. ChlR1 depletion also causes accumulation of DNA damage in response to cisplatin, leading to a significant delay in resolution of DNA damage. We also report that ChlR1-depleted cells display defects in the repair of double-strand breaks induced by the I-PpoI endonuclease and bleomycin. Furthermore, we demonstrate that ChlR1-depeleted cells show significant delays in replication recovery after cisplatin treatment. Taken together, our results indicate that ChlR1 plays an important role in efficient DNA repair during DNA replication, which may facilitate efficient establishment of sister chromatid cohesion.

Keywords: ChlR1 DNA helicase; DNA damage; DNA replication; Replication recovery; Sister chromatid cohesion; Warsaw breakage syndrome.

Publication types

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

MeSH terms

  • Chromatids / drug effects
  • Chromatids / metabolism
  • Cisplatin / toxicity
  • Cross-Linking Reagents / toxicity
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • DNA Damage*
  • DNA End-Joining Repair
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Replication*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • RNA, Small Interfering

Substances

  • Cross-Linking Reagents
  • RNA, Small Interfering
  • DNA Helicases
  • DDX11 protein, human
  • DEAD-box RNA Helicases
  • Cisplatin