State/Key Laboratory of Microbial Technology, Shandong University, 72 Jimo Binhai Road, Qingdao 266237, China.
Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, 30 Qingquan Road, Yantai 264005, China.
Int J Mol Sci. 2022 Aug 27;23(17):9730. doi: 10.3390/ijms23179730.
DNA Holliday junction (HJ) is a four-way stranded DNA intermediate that formed in replication fork regression, homology-dependent repair and mitosis, performing a significant role in genomic stability. Failure to remove HJ can induce an acceptable replication fork stalling and DNA damage in normal cells, leading to a serious chromosomal aberration and even cell death in HJ nuclease-deficient tumor cells. Thus, HJ is becoming an attractive target in cancer therapy. However, the development of HJ-targeting ligand faces great challenges because of flexile cavities on the center of HJs. This review introduces the discovery history of HJ, elucidates the formation and dissociation procedures of HJ in corresponding bio-events, emphasizes the importance of prompt HJ-removing in genome stability, and summarizes recent advances in HJ-based ligand discovery. Our review indicate that target HJ is a promising approach in oncotherapy.
DNA 异源双链连接（HJ）是一种四股链 DNA 中间体，存在于复制叉回退、同源依赖修复和有丝分裂中，在基因组稳定性中发挥重要作用。如果不能去除 HJ，正常细胞中会出现可接受的复制叉停滞和 DNA 损伤，导致严重的染色体畸变，甚至在 HJ 核酸酶缺陷型肿瘤细胞中导致细胞死亡。因此，HJ 成为癌症治疗的一个有吸引力的靶点。然而，由于 HJ 中心的柔性腔，HJ 靶向配体的开发面临巨大挑战。本文介绍了 HJ 的发现历史，阐明了 HJ 在相应生物事件中的形成和解离过程，强调了在基因组稳定性中快速去除 HJ 的重要性，并总结了基于 HJ 的配体发现的最新进展。我们的综述表明，靶向 HJ 是肿瘤治疗的一种有前途的方法。
