DNA repair proteins are critical to the maintenance of genomic integrity. Specific types of genotoxic factors, including reactive oxygen species generated during normal cellular metabolism or as a result of exposure to exogenous oxidative agents, frequently leads to "ragged" single-strand DNA breaks. The latter exhibits abnormal free DNA ends containing either a 5'-hydroxyl or 3'-phosphate requiring correction by the dual function enzyme, polynucleotide kinase phosphatase (PNKP), before DNA polymerase and ligation reactions can occur to seal the break. Pnkp gene deletion during early murine development leads to lethality; in contrast, the role of PNKP in adult mice is unknown. To investigate the latter, we used an inducible conditional mutagenesis approach to cause global disruption of the Pnkp gene in adult mice. This resulted in a premature aging-like phenotype, characterized by impaired growth of hair follicles, seminiferous tubules, and neural progenitor cell populations. These results point to an important role for PNKP in maintaining the normal growth and survival of these murine progenitor populations.

中文翻译：

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PNKP 是维持成年小鼠祖细胞群完整性所必需的。

DNA 修复蛋白对于维持基因组完整性至关重要。特定类型的基因毒性因子，包括在正常细胞代谢过程中产生的活性氧或由于暴露于外源性氧化剂，经常导致“参差不齐”的单链 DNA 断裂。后者表现出含有 5'-羟基或 3'-磷酸盐的异常游离 DNA 末端，需要通过双功能酶多核苷酸激酶磷酸酶 (PNKP) 进行校正，然后才能发生 DNA 聚合酶和连接反应以密封断裂。小鼠早期发育过程中的Pnkp基因缺失导致致死性；相反，PNKP 在成年小鼠中的作用尚不清楚。为了调查后者，成年小鼠的基因。这导致了过早衰老样表型，其特征是毛囊、曲细精管和神经祖细胞群的生长受损。这些结果表明 PNKP 在维持这些鼠祖细胞群的正常生长和存活方面具有重要作用。