Eugen-Olsen Rasmus A B, Hariprakash Judith M, Oestergaard Vibe H, Regenberg Birgitte
Department of Biology, University of Copenhagen, Copenhagen, DK-2200 Copenhagen N, Denmark.
Nucleic Acids Res. 2025 Feb 27;53(5). doi: 10.1093/nar/gkaf122.
Recent research reveals that eukaryotic genomes form circular DNA from all parts of their genome, some large enough to carry whole genes. In organisms like yeast and in human cancers, it is often observed that extrachromosomal circular DNA (eccDNA) benefits the individual cell by providing resources for rapid cellular growth. However, our comprehension of eccDNA remains incomplete, primarily due to their transient nature. Early studies suggest they arise when DNA breaks and is subsequently repaired incorrectly. In this review, we provide an overview of the evidence for molecular mechanisms that lead to eccDNA formation in human cancers and yeast, focusing on nonhomologous end joining, alternative end joining, and homologous recombination repair pathways. Furthermore, we present hypotheses in the form of molecular eccDNA formation models and consider cellular conditions which may affect eccDNA generation. Finally, we discuss the framework for future experimental evidence.
最近的研究表明，真核生物基因组会从其基因组的各个部分形成环状DNA，其中一些环状DNA大到足以携带完整的基因。在酵母等生物体以及人类癌症中，经常观察到染色体外环状DNA（eccDNA）通过为细胞快速生长提供资源而使单个细胞受益。然而，我们对eccDNA的理解仍然不完整，主要是由于它们的短暂性。早期研究表明，它们是在DNA断裂并随后被错误修复时产生的。在这篇综述中，我们概述了导致人类癌症和酵母中eccDNA形成的分子机制的证据，重点关注非同源末端连接、替代末端连接和同源重组修复途径。此外，我们以分子eccDNA形成模型的形式提出假设，并考虑可能影响eccDNA产生的细胞条件。最后，我们讨论了未来实验证据的框架。
