Kurchatov Institute National Research Centre, Moscow, 123182, Russia.
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
Biochemistry (Mosc). 2023 Aug;88(8):1139-1155. doi: 10.1134/S0006297923080084.
Transmission of genetic information depends on successful completion of DNA replication. Genomic DNA is subjected to damage on a daily basis. DNA lesions create obstacles for DNA polymerases and can lead to the replication blockage, formation of DNA breaks, cell cycle arrest, and apoptosis. Cells have evolutionary adapted to DNA damage by developing mechanisms allowing elimination of lesions prior to DNA replication (DNA repair) and helping to bypass lesions during DNA synthesis (DNA damage tolerance). The second group of mechanisms includes the restart of DNA synthesis at the sites of DNA damage by DNA primase-polymerase PrimPol. Human PrimPol was described in 2013. The properties and functions of this enzyme have been extensively studied in recent years, but very little is known about the regulation of PrimPol and association between the enzyme dysfunction and diseases. In this review, we described the mechanisms of human PrimPol regulation in the context of DNA replication, discussed in detail interactions of PrimPol with other proteins, and proposed possible pathways for the regulation of human PrimPol activity. The article also addresses the association of PrimPol dysfunction with human diseases.
遗传信息的传递取决于 DNA 复制的成功完成。基因组 DNA 每天都会受到损伤。DNA 损伤会给 DNA 聚合酶造成障碍，导致复制受阻、DNA 断裂形成、细胞周期停滞和细胞凋亡。细胞通过进化，发展出了在 DNA 复制前清除损伤（DNA 修复）的机制，并在 DNA 合成过程中帮助绕过损伤（DNA 损伤容忍），从而适应 DNA 损伤。第二类机制包括由 PrimPol 引发酶 - 聚合酶在 DNA 损伤部位重新启动 DNA 合成。人类 PrimPol 于 2013 年被描述。近年来，该酶的性质和功能得到了广泛研究，但对 PrimPol 的调控以及酶功能障碍与疾病之间的关联知之甚少。在这篇综述中，我们描述了人类 PrimPol 在 DNA 复制背景下的调控机制，详细讨论了 PrimPol 与其他蛋白质的相互作用，并提出了人类 PrimPol 活性调控的可能途径。文章还探讨了 PrimPol 功能障碍与人类疾病的关联。
