Boldinova Elizaveta O, Kruchinin Alexander A, Kamzeeva Polina N, Aralov Andrey V, Makarova Alena V
Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilova St., 119334 Moscow, Russia.
National Research Center "Kurchatov Institute", Kurchatov sq. 1, 123182 Moscow, Russia.
Int J Mol Sci. 2025 Jul 16;26(14):6796. doi: 10.3390/ijms26146796.
PrimPol is a human DNA primase and DNA polymerase involved in DNA damage tolerance in both nuclei and mitochondria. PrimPol restarts stalled replication forks by synthesizing DNA primers de novo and also possesses DNA translesion activity (TLS activity). PrimPol efficiently and relatively accurately bypasses several DNA lesions including 8-oxoguanine, thymine glycol and 5-formyluracil. In this work, we showed that PrimPol possesses efficient and accurate TLS activity across 8-oxoadenine, another common DNA lesion caused by oxidative stress. The accuracy of PrimPol on DNA with 8-oxoA was significantly higher compared to DNA containing 8-oxoG. Replacement of Mg ions with Mn stimulated activity of PrimPol on DNA with 8-oxoA and 8-oxoG as well as undamaged A in a sequence-dependent manner by the lesion skipping (or template scrunching) mechanism. Altogether, our data support the idea that PrimPol possesses efficient TLS activity across a wide range of DNA lesions caused by oxidative stress.
PrimPol是一种人类DNA引发酶和DNA聚合酶，参与细胞核和线粒体中的DNA损伤耐受。PrimPol通过从头合成DNA引物来重新启动停滞的复制叉，并且还具有DNA跨损伤活性（TLS活性）。PrimPol能高效且相对准确地绕过多种DNA损伤，包括8-氧代鸟嘌呤、胸腺嘧啶乙二醇和5-甲酰尿嘧啶。在这项研究中，我们发现PrimPol对另一种由氧化应激导致的常见DNA损伤——8-氧代腺嘌呤，具有高效且准确的TLS活性。与含有8-氧代鸟嘌呤的DNA相比，PrimPol对含有8-氧代腺嘌呤的DNA的准确性显著更高。用锰取代镁，通过损伤跳跃（或模板挤压）机制以序列依赖的方式刺激了PrimPol对含有8-氧代腺嘌呤和8-氧代鸟嘌呤的DNA以及未损伤腺嘌呤的活性。总之，我们的数据支持了PrimPol对由氧化应激导致的广泛DNA损伤具有高效TLS活性这一观点。
