A mobile genetic element-derived primase-polymerase harbors multiple activities implicated in DNA replication and repair

IF 13.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nucleic Acids Research Pub Date : 2025-01-11 DOI:10.1093/nar/gkae1318

Pan Fu, Yuwei Wang, Yanqiu Liu, Zhenhao Han, Zhangzhong Peng, Linfeng Liu, Wenyuan Han

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Abstract

Primase-polymerases (PrimPols) play divergent functions from DNA replication to DNA repair in all three life domains. In archaea and bacteria, numerous and diverse PPs are encoded by mobile genetic elements (MGEs) and act as the replicases for their MGEs. However, their varying activities and functions are not fully understood. In this study, we characterized a group of PrimPols that are genetically associated with prokaryotic argonaute proteins (pAgos). The pAgo-associated PrimPol (AgaPP) is likely derived from a MGE. AgaPP has polymerase and primase activities and physically interacts with a helicase encoded by its downstream gene, suggesting that they constitute a functional replication module. Further, AgaPP performs translesion DNA synthesis, terminal transfer and microhomology-mediated end joining (MMEJ), showing striking similarity to human DNA repair polymerase θ. AgaPP can promote the MMEJ repair of Cas9-induced double-stranded DNA breaks and increase cell survival post DNA damage in Escherichia coli. In addition, the MMEJ activity of AgaPP can be repurposed to assist DNA assembly in vitro. Together, the findings reveal dual role of AgaPP in both DNA replication and repair.

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一种可移动的遗传元件衍生的引物聚合酶在DNA复制和修复中具有多种活性

引物聚合酶（PrimPols）在DNA复制和DNA修复这三个生命域中发挥着不同的功能。在古细菌和细菌中，大量不同的PPs被移动遗传元件（MGEs）编码，并作为其移动遗传元件的复制酶。然而，它们不同的活动和功能尚未被完全了解。在这项研究中，我们鉴定了一组与原核argonaute蛋白（pAgos）遗传相关的primpol。与pago相关的PrimPol （AgaPP）可能来源于MGE。AgaPP具有聚合酶和引物酶活性，并与其下游基因编码的解旋酶相互作用，表明它们构成了一个功能性复制模块。此外，AgaPP具有翻译DNA合成、末端转移和微同源介导的末端连接（MMEJ）功能，与人类DNA修复聚合酶θ具有惊人的相似性。AgaPP可以促进MMEJ修复cas9诱导的双链DNA断裂，提高大肠杆菌DNA损伤后的细胞存活率。此外，AgaPP的MMEJ活性可以用于辅助体外DNA组装。总之，这些发现揭示了AgaPP在DNA复制和修复中的双重作用。

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来源期刊

Nucleic Acids Research 生物-生化与分子生物学

CiteScore

27.10

自引率

4.70%

发文量

1057

审稿时长

2 months

期刊介绍： Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.