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DNA helicases and their roles in cancer
DNA Repair ( IF 3.0 ) Pub Date : 2020-10-17 , DOI: 10.1016/j.dnarep.2020.102994
Srijita Dhar , Arindam Datta , Robert M. Brosh

DNA helicases, known for their fundamentally important roles in genomic stability, are high profile players in cancer. Not only are there monogenic helicase disorders with a strong disposition to cancer, it is well appreciated that helicase variants are associated with specific cancers (e.g., breast cancer). Flipping the coin, DNA helicases are frequently overexpressed in cancerous tissues and reduction in helicase gene expression results in reduced proliferation and growth capacity, as well as DNA damage induction and apoptosis of cancer cells. The seminal roles of helicases in the DNA damage and replication stress responses, as well as DNA repair pathways, validate their vital importance in cancer biology and suggest their potential values as targets in anti-cancer therapy. In recent years, many laboratories have characterized the specialized roles of helicase to resolve transcription-replication conflicts, maintain telomeres, mediate cell cycle checkpoints, remodel stalled replication forks, and regulate transcription. In vivo models, particularly mice, have been used to interrogate helicase function and serve as a bridge for preclinical studies that may lead to novel therapeutic approaches. In this review, we will summarize our current knowledge of DNA helicases and their roles in cancer, emphasizing the latest developments.



中文翻译:

DNA解旋酶及其在癌症中的作用

DNA解旋酶以其在基因组稳定性中的根本重要作用而闻名,是癌症的重要角色。不仅存在单基因解旋酶疾病,对癌症的抵抗力强,而且众所周知,解旋酶变异体与特定癌症有关(例如, 乳腺癌)。翻转硬币,DNA解旋酶通常在癌组织中过表达,解旋酶基因表达的减少导致癌细胞的增殖和生长能力降低,以及DNA损伤诱导和凋亡。解旋酶在DNA损伤和复制应激反应以及DNA修复途径中的重要作用,证实了它们在癌症生物学中的至关重要性,并暗示了它们在抗癌治疗中的潜在价值。近年来,许多实验室已将解旋酶在解决转录-复制冲突,维持端粒,介导细胞周期检查点,重塑停滞的复制叉和调节转录的特殊作用中发挥了重要作用。体内这些模型,特别是小鼠,已被用于询问解旋酶功能,并作为临床前研究的桥梁,可能会导致新的治疗方法。在这篇综述中,我们将总结我们目前对DNA解旋酶的了解及其在癌症中的作用,并重点介绍最新进展。

更新日期:2020-11-02
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