DNA Resonance Research Foundation, San Diego, CA 92111, USA.
OAK, Inc., Grants Pass, OR 97526, USA.
Int J Mol Sci. 2024 Oct 15;25(20):11050. doi: 10.3390/ijms252011050.
Purine stretches, sequences of adenine (A) and guanine (G) in DNA, play critical roles in binding regulatory protein factors and influence gene expression by affecting DNA folding. This study investigates the relationship between purine stretches and cancer development, considering the aromaticity of purines, quantified by methods like Hückel's rule and NICS calculations, and the importance of the flanking sequence context. A pronounced avoidance of long purine stretches by typical cancer mutations was observed in public data on the intergenic regions of cancer patients, suggesting a role of intergenic sequences in chromatin reorganization and gene regulation. A statistically significant shortening of purine stretches in cancerous tumors ( value < 0.0001) was found. The insights into the aromatic nature of purines and their stacking energies explain the role of purine stretches in DNA structure, contributing to their role in cancer progression. This research lays the groundwork for understanding the nature of purine stretches, emphasizing their importance in gene regulation and chromatin restructuring, and offers potential avenues for novel cancer therapies and insights into cancer etiology.
嘌呤延伸，即 DNA 中的腺嘌呤（A）和鸟嘌呤（G）序列，在结合调控蛋白因子方面发挥着关键作用，并通过影响 DNA 折叠来影响基因表达。本研究考虑了嘌呤的芳香性，通过 Hückel 规则和 NICS 计算等方法进行量化，并考虑了侧翼序列上下文的重要性，调查了嘌呤延伸与癌症发展之间的关系。在癌症患者的基因间区的公共数据中观察到典型癌症突变明显避免长嘌呤延伸，这表明基因间序列在染色质重排和基因调控中发挥作用。在癌症肿瘤中发现嘌呤延伸明显缩短（ value < 0.0001）。对嘌呤芳香性质及其堆积能的深入了解解释了嘌呤延伸在 DNA 结构中的作用，有助于它们在癌症进展中的作用。这项研究为理解嘌呤延伸的本质奠定了基础，强调了它们在基因调控和染色质重构中的重要性，并为新的癌症治疗方法和癌症病因学提供了潜在的途径。
