Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2021 Jan 18;22(2):911. doi: 10.3390/ijms22020911.
Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner.
脱氧核糖核酸（DNA）复制可以分为三个主要步骤：起始、延伸和终止。每次人类细胞分裂，这些步骤都必须反复进行。DNA 复制的中断会导致基因组不稳定，导致点突变或更大的染色体异常，如重排的积累。虽然癌症是与基因组不稳定最相关的疾病类型，但几种具有功能失调的 DNA 复制的先天性疾病也会导致类似的 DNA 改变。在这篇综述中，我们讨论了所有由于复制基因中致病性变异导致的先天性疾病，这些基因涉及异常复制体组装、起点激活和 DNA 合成的各个方面。对于每种情况，我们描述了它们的临床表型以及旨在确定疾病功能机制的分子研究，包括对基因组稳定性的评估。通过比较和对比这些疾病，我们希望阐明在不同步骤中断 DNA 复制如何以一种令人惊讶的细胞类型特异性方式影响人类健康。
