揭示不对称 DNA 复制的复杂性:核糖核苷酸图谱技术及其他方面的进展。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Alberto Bugallo , Mónica Segurado
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引用次数: 0

摘要

DNA 复制是细胞增殖的基本过程,由涉及前导链和滞后链合成的复杂机制控制。在真核生物中,典型的 DNA 复制发生在细胞周期的 S 期,由复制机制的各种成分在称为复制起源的部位进行。前导链和滞后链表现出不同的复制动态,前导链的复制相对简单,而滞后链的合成复杂,涉及冈崎片段的成熟。DNA合成的核心是DNA聚合酶,其中Polα、Polε和Polδ起着关键作用,它们在复制过程中各司其职。值得注意的是,前导链和滞后链由不同的聚合酶进行复制,促进了 DNA 复制中的分工。了解不对称 DNA 复制的酶学一直是一项挑战,而依靠核糖核苷酸结合和新一代测序技术的方法则能提供全面的见解。这些方法(如 HydEn-seq、PU-seq、核糖-seq 和 emRiboSeq)有助于深入了解聚合酶活性和链合成,有助于了解 DNA 复制动态。最新进展包括核糖核苷酸切除修复的新型条件突变体、酶裂解替代方法和统一的数据分析管道。在使技术适应不同生物、研究非典型聚合酶和探索新的测序平台方面的进一步发展,为扩大我们对 DNA 复制动态的了解带来了希望。将链特异性信息整合到单细胞研究中,可为酶学提供新的见解,为修复和复制生物学的未来研究和应用开辟道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unraveling the complexity of asymmetric DNA replication: Advancements in ribonucleotide mapping techniques and beyond

DNA replication is a fundamental process for cell proliferation, governed by intricate mechanisms involving leading and lagging strand synthesis. In eukaryotes, canonical DNA replication occurs during the S phase of the cell cycle, facilitated by various components of the replicative machinery at sites known as replication origins. Leading and lagging strands exhibit distinct replication dynamics, with leading strand replication being relatively straightforward compared to the complex synthesis of lagging strands involving Okazaki fragment maturation. Central to DNA synthesis are DNA polymerases, with Polα, Polε, and Polδ playing pivotal roles, each specializing in specific tasks during replication. Notably, leading and lagging strands are replicated by different polymerases, contributing to the division of labor in DNA replication. Understanding the enzymology of asymmetric DNA replication has been challenging, with methods relying on ribonucleotide incorporation and next-generation sequencing techniques offering comprehensive insights. These methodologies, such as HydEn-seq, PU-seq, ribose-seq, and emRiboSeq, offer insights into polymerase activity and strand synthesis, aiding in understanding DNA replication dynamics. Recent advancements include novel conditional mutants for ribonucleotide excision repair, enzymatic cleavage alternatives, and unified pipelines for data analysis. Further developments in adapting techniques to different organisms, studying non-canonical polymerases, and exploring new sequencing platforms hold promise for expanding our understanding of DNA replication dynamics. Integrating strand-specific information into single-cell studies could offer novel insights into enzymology, opening avenues for future research and applications in repair and replication biology.

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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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