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 end-joining (NHEJ), wherein the two DNA ends are re-joined. 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 λ) and mu (Pol μ) promote DNA end-joining. Here, we show that DNA polymerase beta (Pol β), another member of the X family of DNA polymerases, plays a role in aNHEJ. In the absence of DNA Pol β, fewer small deletions are observed. In addition, depletion of Pol β 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 β in functions in aNHEJ and provide mechanistic insight into its role in this process.

中文翻译：

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DNA聚合酶beta参与DNA末端连接

DNA双链断裂（DSB）是最有害的病变之一，如果不加以修复，会导致细胞死亡，基因组不稳定和致癌作用。细胞通过两种途径与DSB战斗：同源重组（HR）和非同源末端连接（NHEJ），其中两个DNA末端重新连接。近来，已经报道了备用NHEJ途径，其被称为替代NHEJ（aNHEJ），其连接末端但导致缺失和插入。NHEJ需要加工酶，包括核酸酶和聚合酶，尽管对这些酶的作用了解甚少。新兴证据表明，X家族DNA聚合酶lambda（Polλ）和mu（Polμ）促进DNA末端连接。在这里，我们显示DNA聚合酶β（Polβ），DNA聚合酶X家族的另一个成员，在aNHEJ中发挥作用。在没有DNA Polβ的情况下，观察到较少的小缺失。另外，由于DSB的修复缺陷，Polβ的耗尽导致细胞对博来霉素和DNA蛋白激酶催化亚基抑制剂的敏感性。总而言之，我们的结果表明，Polβ在aNHEJ中起作用，并提供了对其在此过程中的作用的机械观察。