Possible association of BLM in decreasing DNA double strand breaks during DNA replication.

Bloom’s syndrome (BS) is a rare genetic disorder and the cells from BS patients show genomic instability and an increased level of sister chromatid exchange (SCE). We generated BLM–/– and BLM–/–/RAD54–/– DT40 cells from the chicken B-lymphocyte line DT40. The BLM–/– DT40 cells showed higher sensitivity to methyl methanesulfonate and elevated levels of SCE as expected. The targeted integration frequency was also increased remarkably in BLM–/– cells. The SCE frequency increase in BLM–/– cells was considerably reduced and the enhanced targeted integration observed in BLM–/– cells was almost completely abolished in BLM–/–/RAD54–/– cells, indicating that a large portion of the SCE in BLM–/– cells occurs via homologous recombination, and homologous recombination events increase with the defect of BLM function. The BLM–/–/RAD54–/– cells showed a slow growth phenotype and an increased incidence of chromosome-type breaks/gaps while each single mutant showed relatively small numbers of chromosome-type breaks/gaps.