Chandrasekhar Soumya, Swope Thomas P, Fadaei Fatemeh, Hollis Daniel R, Bricker Rachel, Houser Draven, Portman John J, Schmidt Thorsten L
Department of Physics, Kent State University, Kent, OH, 44242, USA.
bioRxiv. 2024 Nov 27:2024.02.14.579968. doi: 10.1101/2024.02.14.579968.
In all biological systems, DNA is under high mechanical stress from bending and twisting. For example, DNA is tightly bent in nucleosome complexes, virus capsids, bacterial chromosomes, or complexes with transcription factors that regulate gene expression. A structurally and mechanically accurate model of DNA is therefore necessary to understand some of the most fundamental molecular mechanisms in biology including DNA packaging, replication, transcription and gene regulation. An iconic feature of DNA is its double helical nature with an average repeat of ~10.45 base pairs per turn, which is commonly believed to be independent of curvature. We developed a ligation assay on nicked DNA circles of variable curvature that reveals a strong unwinding of DNA to over 11 bp/turn for radii around 3-4 nm. Our work constitutes a major modification of the standard mechanical model of DNA and requires reassessing the molecular mechanisms and energetics of all processes involving tightly bent DNA.
在所有生物系统中,DNA都承受着来自弯曲和扭转的高机械应力。例如,DNA在核小体复合物、病毒衣壳、细菌染色体或与调节基因表达的转录因子形成的复合物中会紧密弯曲。因此,为了理解生物学中一些最基本的分子机制,包括DNA包装、复制、转录和基因调控,需要一个结构和力学上准确的DNA模型。DNA的一个标志性特征是其双螺旋结构,平均每圈约有10.45个碱基对重复,通常认为这与曲率无关。我们在具有可变曲率的带切口DNA环上开发了一种连接测定法,结果显示,对于半径约为3 - 4纳米的情况,DNA会强烈解旋至超过11个碱基对/圈。我们的工作对DNA的标准力学模型进行了重大修正,需要重新评估所有涉及紧密弯曲DNA的过程的分子机制和能量学。