BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance

RAD51 is one of six mitotic human homologs of the E. coli RecA protein (RAD 51-Paralogs) that play a central role in homologous recombination and repai r of DNA double-strand breaks (DSBs). Here we demonstrate that RAD51 is imp ortant for resistance to cisplatin and mitomycin C in cells expressing the BCR/ABL oncogenic tyrosine kinase. BCR/ABL significantly enhances the expre ssion of RAD51 and several RAD51-Paralogs. RAD51 overexpression is mediated by a STAT5-dependent transcription as well as by inhibition of caspase-3-d ependent cleavage. Phosphorylation of the RAD51 Tyr-315 residue by BCR/ABL appears essential for enhanced DSB repair and drug resistance. Induction of the mammalian RecA homologs establishes a unique mechanism for DNA damage resistance in mammalian cells transformed by an oncogenic tyrosine kinase.