Role of condensates in modulating DNA repair pathways and its implication for chemoresistance.
Role of condensates in modulating DNA repair pathways and its implication for chemoresistance.
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缩合物在调节DNA修复途径中的作用及其与化疗耐药性的关系。
DOI：
10.1016/j.jbc.2023.104800
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发表时间：
2023-06
影响因子：
4.8
通讯作者：
Tell, Gianluca
中科院分区：
文献类型：
--
作者：
Dall'Agnese, Giuseppe;Dall'Agnese, Alessandra;Banani, Salman F.;Codrich, Marta;Malfatti, Matilde Clarissa;Antoniali, Giulia;Tell, Gianluca
对于细胞而言，修复诸如DNA双链和单链断裂等DNA损伤至关重要，因为未修复的DNA会损害遗传完整性，有可能导致细胞死亡或引发癌症。细胞拥有多种DNA损伤修复途径，这些途径一直是遗传学、生物化学和结构学详细研究的对象。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体中，而且凝聚体可能还会通过浓缩用于治疗各种癌症的基因毒性物质，从而导致DNA损伤。在此，我们总结了生物分子凝聚体的关键特征，并指出它们在DNA双链断裂修复中所起的作用。我们还阐述了相关证据，这些证据表明凝聚体可能参与其他类型DNA损伤的修复，包括单链DNA断裂、核苷酸修饰（如错配碱基和氧化碱基）以及大分子损伤等。最后，我们探讨了鉴于凝聚体的特性目前可以研究的新旧谜题，其中包括化学抗性机制。
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.
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