人类 PrimPol 跨 DNA 发夹合成 DNA

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2024-08-08 DOI:10.1016/j.dnarep.2024.103741

Elizaveta O. Boldinova , Andrey G. Baranovskiy , Daria Esyunina , Tahir H. Tahirov , Alena V. Makarova

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引用次数: 0

摘要

PrimPol 是一种人类 DNA 引物酶，通过在 DNA 损伤和非典型 DNA 结构下游重新启动 DNA 复制，参与 DNA 损伤耐受途径。PrimPol 与 DNA 的活性和亲和力取决于 PrimPol 与复制蛋白 A（RPA）的相互作用。在这项工作中，我们报告了 PrimPol 复制茎长度为 5-9 碱基对（bp）的 DNA 发夹的内在能力，但会明显暂停 DNA 合成。RPA极大地刺激了PrimPol跨倒置DNA重复序列的DNA合成。此外，删除 C 端 RPA 结合基团（RBM）可促进 DNA 发夹旁路，并使其独立于 RPA。这项工作支持了这样一种观点，即 RBM 是 PrimPol 的负调控因子，它与 RPA 的相互作用是达到完全活性状态所必需的。

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DNA synthesis across DNA hairpins by human PrimPol

PrimPol is a human DNA primase involved in DNA damage tolerance pathways by restarting DNA replication downstream of DNA lesions and non-canonical DNA structures. Activity and affinity to DNA relays on the interaction of PrimPol with replication protein A (RPA). In this work, we report that PrimPol has an intrinsic ability to copy DNA hairpins with a stem length of 5–9 base pairs (bp) but shows pronounced pausing of DNA synthesis. RPA greatly stimulates DNA synthesis across inverted DNA repeats by PrimPol. Moreover, deletion of the C-terminal RPA binding motif (RBM) facilitates DNA hairpin bypass and makes it independent of RPA. This work supports the idea that RBM is a negative regulator of PrimPol and its interaction with RPA is required to achieve the fully active state.

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来源期刊

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.