Laboratory of Molecular Biology and DNA repair, Department of Medicine, University of Udine, Udine, Italy; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
J Biol Chem. 2023 Jun;299(6):104800. doi: 10.1016/j.jbc.2023.104800. Epub 2023 May 9.
For cells, it is important to repair DNA damage, such as double-strand and single-strand DNA breaks, because unrepaired DNA can compromise genetic integrity, potentially leading to cell death or cancer. Cells have multiple DNA damage repair pathways that have been the subject of detailed genetic, biochemical, and structural studies. Recently, the scientific community has started to gain evidence that the repair of DNA double-strand breaks may occur within biomolecular condensates and that condensates may also contribute to DNA damage through concentrating genotoxic agents used to treat various cancers. Here, we summarize key features of biomolecular condensates and note where they have been implicated in the repair of DNA double-strand breaks. We also describe evidence suggesting that condensates may be involved in the repair of other types of DNA damage, including single-strand DNA breaks, nucleotide modifications (e.g., mismatch and oxidized bases), and bulky lesions, among others. Finally, we discuss old and new mysteries that could now be addressed considering the properties of condensates, including chemoresistance mechanisms.
对于细胞来说，修复 DNA 损伤（如双链和单链 DNA 断裂）非常重要，因为未修复的 DNA 会损害遗传完整性，可能导致细胞死亡或癌症。细胞有多种 DNA 损伤修复途径，这些途径一直是详细的遗传、生化和结构研究的主题。最近，科学界开始获得证据表明，DNA 双链断裂的修复可能发生在生物分子凝聚物内，并且凝聚物也可能通过浓缩用于治疗各种癌症的遗传毒性剂来导致 DNA 损伤。在这里，我们总结了生物分子凝聚物的关键特征，并指出了它们在 DNA 双链断裂修复中的作用。我们还描述了一些证据，表明凝聚物可能参与其他类型的 DNA 损伤的修复，包括单链 DNA 断裂、核苷酸修饰（如错配和氧化碱基）和大体积损伤等。最后，我们讨论了一些现在可以考虑凝聚物特性来解决的旧的和新的谜团，包括化学抗性机制。
