PAXX Participates in Base Excision Repair via Interacting with Pol β and Contributes to TMZ Resistance in Glioma Cells.

Non-homologous end joining (NHEJ) is one of the major DNA repair pathway in mammalian cell that can ligate a variety of DNA ends. However, how does all NHEJ factors communicate and organize together to achieve the final repair is still not clear. PAralog of XRCC4 and XLF (PAXX) was a new factor identified recently that play an important role in NHEJ. PAXX contributes to efficient NHEJ by interacting with Ku, which is a NHEJ key factor, and PAXX deficiency cause sensitivity to DNA double-strand break repair (DSBR). We observed that PAXX-deficient cells showed slight increase of homologous recombination (HR, which is another major DSBR repair pathways in mammalian cells). More importantly, we found that PAXX contributes to base excision repair pathway via interaction of polymerase beta (pol β). Temozolomide (TMZ) is one of the standard chemotherapies widely applied in glioblastoma. However, TMZ resistance and lack of potent chemotherapy agents can substitute TMZ. We observed that PAXX deficiency cause more sensitivity to TMZ-resistant glioma cells. In conclusion, the PAXX contributes to a variety of DNA repair pathways and TMZ resistance. Therefore, inhibition of PAXX may provide a promising way to overcome TMZ resistance and improve TMZ therapeutic effects in glioma treatment.