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 pati ents show genomic instability and an increased level of sister chromatid ex change (SCE). We generated BLM-/- and BLM-/-/RAD54(-/-) DT40 cells from the chicken B-lymphocyte line DT40. The BLM-/- DT40 cells showed higher sensit ivity to methyl methanesulfonate and elevated levels of SCE as expected. Th e targeted integration frequency was also increased remarkably in BLM-/- ce lls. The SCE frequency increase in BLM-/- cells was considerably reduced an d the enhanced targeted integration observed in BLM-/- cells was almost com pletely abolished in BLM-/-/RAD54(-/-) cells, indicating that a large porti on of the SCE in BLM-/- cells occurs via homologous recombination, and homo logous recombination events increase with the defect of BLM function. The B LM-/-/RAD54(-/-) cells showed a slow growth phenotype and an increased inci dence of chromosome-type breaks/gaps while each single mutant showed relati vely small numbers of chromosome-type breaks/ gaps.