Involvement of DNA recombination repair proteins in chromosomal translocations

由电离辐射和化疗药物引起的染色体易位已被证明可导致恶性转化。然而，染色体易位的机制尚不清楚。涉及11q23上MLL基因的染色体易位是与依托泊苷化疗相关的继发性白血病中最常见的染色体异常。DNA损伤信号调节因子ATM的功能障碍会增加11q23染色体易位的发生率。我们发现，在依托泊苷暴露后，ATM缺乏导致MLL基因易位断点簇区（BCR）的DNA重组酶RAD51过度结合。在本研究中，我们发现在依托泊苷暴露后，ATM对RPA2的磷酸化在调节RAD51与MLL基因BCR的结合中起重要作用。

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.