Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
DNA Repair (Amst). 2013 Aug;12(8):620-36. doi: 10.1016/j.dnarep.2013.04.015. Epub 2013 May 16.
DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease.
内源性或外源性遗传毒性剂造成的 DNA 损伤可能以多种形式存在,如果任其持续存在,可能会促进基因组不稳定,并直接导致各种人类疾病,特别是癌症、神经发育异常、免疫缺陷和早衰。为了避免这些有害后果,细胞已经进化出一系列 DNA 修复途径,这些途径通常执行一个多步骤的过程来解决特定的 DNA 损伤,并维持基因组的完整性。为了充分了解不同 DNA 修复系统的生物学贡献,人们必须记住它们运作的细胞环境。例如,人体由非分裂和分裂细胞类型组成,包括大脑中的神经元和神经胶质细胞。本文描述了不同 DNA 修复途径的分子机制,并回顾了它们在非分裂和分裂细胞中的作用,着眼于这些途径如何调节神经疾病的发展。