DNA polymerase beta participates in DNA End-joining

摘要

DNA double strand breaks (DSBs) are one of the most deleterious lesions and if left unrepaired, they lead to cell death, genomic instability and carcinogenesis. Cells combat DSBs by two pathways: homologous recombination (HR) and non-homologous endjoining (NHEJ), wherein the two DNA ends are rejoined. Recently a back-up NHEJ pathway has been reported and is referred to as alternative NHEJ (aNHEJ), which joins ends but results in deletions and insertions. NHEJ requires processing enzymes including nucleases and polymerases, although the roles of these enzymes are poorly understood. Emerging evidence indicates that X family DNA polymerases lambda (Pol lambda) and mu (Pol mu) promote DNA endjoining. Here, we show that DNA polymerase beta (Pol beta), another member of the X family of DNA polymerases, plays a role in aNHEJ. In the absence of DNA Pol beta, fewer small deletions are observed. In addition, depletion of Pol beta results in cellular sensitivity to bleomycin and DNA protein kinase catalytic subunit inhibitors due to defective repair of DSBs. In summary, our results indicate that Pol beta in functions in aNHEJ and provide mechanistic insight into its role in this process.