Analysis of homologous DNA recombination using the chicken B-lymphocyte line

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The department now has a solid base of very active research in the field of cellular response to DNA damage, including DNA repair, DNA Recombination, apoptosis, and cell cycle regulation.(1) We have successfully generated DT40 mutants deficient in each of all the RAD52 epistasis group genes, and have found they are indeed involved in HR including gene targeting.(2) We found that depletion of either Rad51 or Mrell causes chromosomal breaks like wild-type DT40 cells irradiated with X-rays. Since HR is involved with dsb repair, these observations suggest that dsbs occur frequently during the cell cycle in vertebrate cells and that HR is responsible for repairing such DNA damage.(3) We reported significantly low levels of SCEs in all HR-deficient cell lines. This was an important finding as it established a direct correlation between HR-mediated repair and SCEs for the first time.(4) Two major repair pathways exist in eukaryotes to tackle DNA dsbs : Non-homologous end-joining (NHEJ) and HR.We showed that homologous DNA recombiantion can mediate interactions between sister chromatids but not homologous chromosomes for DNA double-strand break repair in vertebrate cells.Our scudies are relevant to analysis of oncogenesis caused by genetic instability, cancer therapy, and development of methods for gene therapy.