细菌复制原点 BUS 促进碱基捕获。

The bacterial replication origin BUS promotes nucleobase capture.

机构信息

Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle Upon Tyne, NE2 4AX, UK.

Centre for Molecular Cell Biology, School of Biological and Behavioural Sciences, Queen Mary University of London, Newark Street, London, E1 2AT, UK.

出版信息

Nat Commun. 2023 Dec 14;14(1):8339. doi: 10.1038/s41467-023-43823-w.

DOI:10.1038/s41467-023-43823-w

PMID:38097584

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10721633/

Abstract

Genome duplication is essential for the proliferation of cellular life and this process is generally initiated by dedicated replication proteins at chromosome origins. In bacteria, DNA replication is initiated by the ubiquitous DnaA protein, which assembles into an oligomeric complex at the chromosome origin (oriC) that engages both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) to promote DNA duplex opening. However, the mechanism of DnaA specifically opening a replication origin was unknown. Here we show that Bacillus subtilis DnaA assembles into a continuous oligomer at the site of DNA melting, extending from a dsDNA anchor to engage a single DNA strand. Within this complex, two nucleobases of each ssDNA binding motif (DnaA-trio) are captured within a dinucleotide binding pocket created by adjacent DnaA proteins. These results provide a molecular basis for DnaA specifically engaging the conserved sequence elements within the bacterial chromosome origin basal unwinding system (BUS).

摘要

基因组复制对于细胞生命的增殖至关重要，这个过程通常是由专门的复制蛋白在染色体起点启动的。在细菌中，DNA 复制由普遍存在的 DnaA 蛋白启动，该蛋白在染色体起点（oriC）组装成一个寡聚体复合物，与双链 DNA（dsDNA）和单链 DNA（ssDNA）结合，促进 DNA 双链体打开。然而，DnaA 特异性打开复制起点的机制尚不清楚。在这里，我们表明枯草芽孢杆菌 DnaA 在 DNA 融解的部位组装成一个连续的寡聚体，从 dsDNA 锚点延伸，与单链 DNA 结合。在这个复合物中，每个 ssDNA 结合基序（DnaA-三联体）的两个核碱基被相邻的 DnaA 蛋白形成的二核苷酸结合口袋捕获。这些结果为 DnaA 特异性结合细菌染色体起点基本解旋系统（BUS）内保守序列元件提供了分子基础。