DNA single-strand breaks (SSBs) are among the most common lesions arising in human cells, with tens to hundreds of thousands arising in each cell, each day. Cells have efficient mechanisms for the sensing and repair of these ubiquitous DNA lesions, but the failure of these processes to rapidly remove SSBs can lead to a variety of pathogenic outcomes. The threat posed by unrepaired SSBs is illustrated by the existence of at least six genetic diseases in which SSB repair (SSBR) is defective, all of which are characterised by neurodevelopmental and/or neurodegenerative pathology. Here, I review current understanding of how SSBs arise and impact on critical molecular processes, such as DNA replication and gene transcription, and their links to human disease.

DNA 单链断裂 (SSB) 是人类细胞中最常见的损伤之一，每个细胞每天都会出现数万到数十万个。细胞具有有效的机制来感知和修复这些普遍存在的 DNA 损伤，但这些过程无法快速去除 SSB，可能会导致各种致病结果。至少有六种 SSB 修复 (SSBR) 有缺陷的遗传性疾病的存在说明了未修复的 SSB 所带来的威胁，所有这些疾病都以神经发育和/或神经退行性病理学为特征。在这里，我回顾了目前对 SSB 如何产生以及对 DNA 复制和基因转录等关键分子过程的影响及其与人类疾病的联系的理解。