Henderson D S, Glover D M
Cancer Research Campaign Laboratories, University of Dundee, UK.
Mutagenesis. 1998 Jan;13(1):57-60. doi: 10.1093/mutage/13.1.57.
Proliferating cell nuclear antigen (PCNA) has several roles in progression through S phase: it is required for the function of DNA polymerases delta and epsilon and physically associates with the structure-specific nuclease FEN-1 that is essential for Okazaki fragment processing. The cyclindependent kinase inhibitor p21 appears to displace FEN-1 from PCNA to inhibit DNA replication and possibly permit participation of PCNA in nucleotide excision repair. Here we show that PCNA is also indispensable for repair of DNA double-strand breaks (DSBs), lesions which are not corrected by excision repair processes. When PCNA-deficient Drosophila mutants are incorporated into a genetic system that induces chromosomal site-specific DSBs upon mobilization of transposable P elements they fail to undertake DSB repair. This has dominant lethal effects: DSBs are converted into chromosome breaks that can be seen at mitosis.
增殖细胞核抗原（PCNA）在S期进程中具有多种作用：它是DNA聚合酶δ和ε发挥功能所必需的，并且与结构特异性核酸酶FEN-1物理结合，而FEN-1对于冈崎片段的加工至关重要。细胞周期蛋白依赖性激酶抑制剂p21似乎将FEN-1从PCNA上置换下来，以抑制DNA复制，并可能使PCNA参与核苷酸切除修复。在此我们表明，PCNA对于DNA双链断裂（DSB）的修复也是不可或缺的，而切除修复过程无法校正这些损伤。当将缺乏PCNA的果蝇突变体纳入一个在转座P元件动员时诱导染色体位点特异性DSB的遗传系统中时，它们无法进行DSB修复。这具有显性致死效应：DSB会转化为在有丝分裂时可见的染色体断裂。
