School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
Biochem Soc Trans. 2011 Dec;39(6):1715-8. doi: 10.1042/BST20110700.
Progeroid laminopathies are characterized by the abnormal processing of lamin A, the appearance of misshapen nuclei, and the accumulation and persistence of DNA damage. In the present article, I consider the contribution of defective DNA damage pathways to the pathology of progeroid laminopathies. Defects in DNA repair pathways appear to be caused by a combination of factors. These include abnormal epigenetic modifications of chromatin that are required to recruit DNA repair pathways to sites of DNA damage, abnormal recruitment of DNA excision repair proteins to sites of DNA double-strand breaks, and unrepairable ROS (reactive oxygen species)-induced DNA damage. At least two of these defective processes offer the potential for novel therapeutic approaches.
早衰性层粘连蛋白病的特征是层粘连 A 的异常加工、畸形核的出现以及 DNA 损伤的积累和持续存在。在本文中，我考虑了有缺陷的 DNA 损伤途径对早衰性层粘连蛋白病病理学的贡献。DNA 修复途径的缺陷似乎是由多种因素共同引起的。这些因素包括染色质的异常表观遗传修饰，这些修饰是将 DNA 修复途径募集到 DNA 损伤部位所必需的；异常募集 DNA 切除修复蛋白到 DNA 双链断裂部位；以及无法修复的 ROS（活性氧）诱导的 DNA 损伤。至少其中两个有缺陷的过程为新的治疗方法提供了潜力。
