Human development and tissue homeostasis depend on the regulated control of cellular proliferation and differentiation. DNA replication is essential to couple genome duplication and cell division with the establishment and maintenance of cellular differentiation programs. In eukaryotes, DNA replication is performed by a large machine known as the ‘replisome,’ which is strictly regulated in a cell cycle-dependent manner. Inherited mutations of replisome components have been identified in a range of genetic conditions characterised by developmental abnormalities and reduced organismal growth in addition to an involvement of the immune and endocrine systems and/or heightened tumour predisposition. Here, we review the current knowledge of the molecular genetics of replisome dysfunction disorders and discuss recent mechanistic insights into their pathogenesis, with a focus on the specific steps of DNA replication affected in these human diseases.

人类发育和组织稳态取决于细胞增殖和分化的调节控制。DNA 复制对于将基因组复制和细胞分裂与细胞分化程序的建立和维持结合起来至关重要。在真核生物中，DNA 复制是由称为“复制体”的大型机器进行的，它以依赖于细胞周期的方式受到严格调控。除了免疫和内分泌系统的参与和/或增强的肿瘤易感性之外，已经在一系列以发育异常和生物体生长减少为特征的遗传病况中鉴定了复制体成分的遗传突变。这里，