Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, U.K.
Biosci Rep. 2023 Jul 26;43(7). doi: 10.1042/BSR20221986.
To pass on genetic information to the next generation, cells must faithfully replicate their genomes to provide copies for each daughter cell. To synthesise these duplicates, cells employ specialised enzymes called DNA polymerases, which rapidly and accurately replicate nucleic acid polymers. However, most polymerases lack the ability to directly initiate DNA synthesis and required specialised replicases called primases to make short polynucleotide primers, from which they then extend. Replicative primases (eukaryotes and archaea) belong to a functionally diverse enzyme superfamily known as Primase-Polymerases (Prim-Pols), with orthologues present throughout all domains of life. Characterised by a conserved catalytic Prim-Pol domain, these enzymes have evolved various roles in DNA metabolism, including DNA replication, repair, and damage tolerance. Many of these biological roles are fundamentally underpinned by the ability of Prim-Pols to generate primers de novo. This review examines our current understanding of the catalytic mechanisms utilised by Prim-Pols to initiate primer synthesis.
为了将遗传信息传递给下一代，细胞必须忠实地复制其基因组，为每个子细胞提供副本。为了合成这些副本，细胞采用了专门的酶，称为 DNA 聚合酶，它可以快速准确地复制核酸聚合物。然而，大多数聚合酶缺乏直接起始 DNA 合成的能力，需要专门的复制酶，称为引发酶，来合成短的多核苷酸引物，然后从引物延伸。复制引发酶（真核生物和古菌）属于功能多样的酶超家族，称为引发酶-聚合酶（Prim-Pols），在生命的所有领域都存在同源物。这些酶的特征是具有保守的催化 Prim-Pol 结构域，在 DNA 代谢中进化出了各种作用，包括 DNA 复制、修复和损伤耐受。其中许多生物学作用的基础是 Prim-Pols 从头生成引物的能力。这篇综述考察了我们目前对 Prim-Pols 用于启动引物合成的催化机制的理解。
