Targeting of Rad51-dependent homologous recombination: implications for the radiation sensitivity of human lung cancer cell lines

Br J Cancer. 2005 Mar 28;92(6):1089-97. doi: 10.1038/sj.bjc.6602457.


The aim of the present work was to study the role of Rad51-dependent homologous recombination in the radiation response of non-small-cell lung cancer (NSCLC) cell lines. A dose- and time-dependent increase in the formation of Rad51 and gamma-H2AX foci with a maximum at about 4 and 1 h after irradiation, followed by a decrease, has been found. The relative fraction of cells with persisting Rad51 foci was 20-30% in radioresistant and 60-80% in radiosensitive cell lines. In comparison, a higher fraction of residual Dsb was evident in cell lines with nonfunctional p53. Transfection with As-Rad51 significantly downregulates radiation-induced formation of Rad51 foci and increases apoptosis, but did not influence the rejoining of DNA double-strand breaks. Interestingly, wortmannin, a well-known inhibitor of nonhomologous end-joining, also inhibits Rad51 foci formation. In general, there was no correlation between the clonogenic survival at 2 Gy and the percentage of initial Rad51 or gamma-H2AX foci after ionising radiation (IR). The most reliable predictive factor for radiosensitivity of NSCLC cell lines was the relative fraction of Rad51 foci remaining at 24 h after IR. Although most of the Rad51 foci are co-localised with gamma-H2AX foci, no correlation of the relative fraction of persisting gamma-H2AX foci and SF2 is evident.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Cell Line, Tumor
  • DNA Repair
  • DNA-Binding Proteins / physiology*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Oligonucleotides, Antisense / pharmacology
  • Rad51 Recombinase
  • Radiation Tolerance
  • Recombination, Genetic*
  • Tumor Suppressor Protein p53 / physiology


  • DNA-Binding Proteins
  • Oligonucleotides, Antisense
  • Tumor Suppressor Protein p53
  • RAD51 protein, human
  • Rad51 Recombinase