Involvement of DNA recombination repair proteins in chromosomal translocations

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Chromosome translocations induced by ionizing radiation and chemotherapeutic agents, has been shown to lead to malignant transformation. However, the mechanism of chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide. Dysfunction of ATM, a DNA damage signaling regulator, increases the incidence of 11q23 chromosome translocations. We showed that ATM deficiency results in the excessive binding of the DNA recombinase RAD51 at the translocation breakpoint cluster region (BCR) of MLL gene after etoposide exposure. In this study, we showed that phosphorylation of RPA2 by ATM plays an important role in the regulation of RAD51 binding to the BCR of MLL gene after etoposide exposure.