Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA.
Department of Biology, Tufts University, Medford, MA, USA.
Mol Cell. 2023 Oct 19;83(20):3622-3641. doi: 10.1016/j.molcel.2023.08.018.
Around 3% of the genome consists of simple DNA repeats that are prone to forming alternative (non-B) DNA structures, such as hairpins, cruciforms, triplexes (H-DNA), four-stranded guanine quadruplexes (G4-DNA), and others, as well as composite RNA:DNA structures (e.g., R-loops, G-loops, and H-loops). These DNA structures are dynamic and favored by the unwinding of duplex DNA. For many years, the association of alternative DNA structures with genome function was limited by the lack of methods to detect them in vivo. Here, we review the recent advancements in the field and present state-of-the-art technologies and methods to study alternative DNA structures. We discuss the limitations of these methods as well as how they are beginning to provide insights into causal relationships between alternative DNA structures, genome function and stability, and human disease.
基因组约有 3%由简单的 DNA 重复序列组成，这些重复序列容易形成替代（非 B）DNA 结构，如发夹、十字形、三链体（H-DNA）、四链体鸟嘌呤四链体（G4-DNA）和其他结构，以及复合 RNA:DNA 结构（例如，R 环、G 环和 H 环）。这些 DNA 结构是动态的，并且有利于双链 DNA 的解旋。多年来，替代 DNA 结构与基因组功能的关联受到缺乏在体内检测它们的方法的限制。在这里，我们回顾了该领域的最新进展，并介绍了研究替代 DNA 结构的最新技术和方法。我们讨论了这些方法的局限性，以及它们如何开始为替代 DNA 结构、基因组功能和稳定性以及人类疾病之间的因果关系提供见解。
