Fink Lauren S, Roell Michaela, Caiazza Emanuela, Lerner Chad, Stamato Thomas, Hrelia Silvana, Lorenzini Antonello, Sell Christian
Department of Pathology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Aging (Albany NY). 2011 Sep;3(9):836-45. doi: 10.18632/aging.100381.
Faithful repair of damaged DNA is a crucial process in maintaining cell viability and function. A multitude of factors and pathways guides this process and includes repair proteins and cell cycle checkpoint factors. Differences in the maintenance of genomic processes are one feature that may contribute to species-specific differences in lifespan. We predicted that 53BP1, a key transducer of the DNA damage response and cell cycle checkpoint control, is highly involved in maintaining genomic stability and may function differently in cells from different species. We demonstrate a difference in the levels and recruitment of 53BP1 in mouse and human cells following DNA damage. In addition, we show that unresolved DNA damage persists more in mouse cells than in human cells, as evidenced by increased numbers of micronuclei. The difference in micronuclei seems to be related to the levels of 53BP1 present in cells. Finally, we present evidence that unresolved DNA damage correlates with species lifespan. Taken together, these studies suggest a link between recruitment of 53BP1, resolution of DNA damage, and increased species lifespan.
受损DNA的忠实修复是维持细胞活力和功能的关键过程。众多因素和途径引导这一过程，包括修复蛋白和细胞周期检查点因子。基因组过程维持方面的差异是一个可能导致物种寿命存在差异的特征。我们预测，53BP1作为DNA损伤反应和细胞周期检查点控制的关键转导因子，在维持基因组稳定性方面高度相关，并且在来自不同物种的细胞中可能发挥不同的作用。我们证明了DNA损伤后，小鼠和人类细胞中53BP1的水平和募集存在差异。此外，我们发现未解决的DNA损伤在小鼠细胞中比在人类细胞中持续时间更长，微核数量增加证明了这一点。微核的差异似乎与细胞中53BP1的水平有关。最后，我们提供证据表明未解决的DNA损伤与物种寿命相关。综上所述，这些研究表明53BP1的募集、DNA损伤的解决与物种寿命延长之间存在联系。
