Backup pathways of NHEJ in cells of higher eukaryotes: cell cycle dependence

Radiother Oncol. 2009 Sep;92(3):310-5. doi: 10.1016/j.radonc.2009.06.024. Epub 2009 Jul 13.


DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) in cells of higher eukaryotes are predominantly repaired by a pathway of non-homologous end joining (NHEJ) utilizing Ku, DNA-PKcs, DNA ligase IV, XRCC4 and XLF/Cernunnos (D-NHEJ) as central components. Work carried out in our laboratory and elsewhere shows that when this pathway is chemically or genetically compromised, cells do not shunt DSBs to homologous recombination repair (HRR) but instead use another form of NHEJ operating as a backup (B-NHEJ). Here I review our efforts to characterize this repair pathway and discuss its dependence on the cell cycle as well as on the growth conditions. I present evidence that B-NHEJ utilizes ligase III, PARP-1 and histone H1. When B-NHEJ is examined throughout the cell cycle, significantly higher activity is observed in G2 phase that cannot be attributed to HRR. Furthermore, the activity of B-NHEJ is compromised when cells enter the plateau phase of growth. Together, these observations uncover a repair pathway with unexpected biochemical constitution and interesting cell cycle and growth factor regulation. They generate a framework for investigating the mechanistic basis of HRR contribution to DSB repair.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / radiation effects
  • DNA Breaks, Double-Stranded / radiation effects*
  • DNA Damage / genetics
  • DNA Damage / radiation effects*
  • DNA Ligases / genetics
  • DNA Ligases / radiation effects
  • DNA Repair / genetics*
  • DNA Repair / radiation effects
  • Eukaryotic Cells / physiology
  • Eukaryotic Cells / radiation effects*
  • Humans
  • Radiation Genetics
  • Radiation, Ionizing
  • Recombination, Genetic
  • Sensitivity and Specificity
  • Signal Transduction


  • DNA Ligases