DNA 复制应激 (DRS) 反应是面对 DNA 复制的内在和外在障碍时维持基因组完整性的重要稳态机制。重要的是，肿瘤细胞中的 DRS 通常显着增加，使得肿瘤依赖于细胞 DRS 反应来生长和存活。 Rad9-Hus1-Rad1 相互作用核孤儿 1 (RHNO1) 是一种参与 DRS 反应的蛋白质，最近已成为癌症的潜在治疗靶点。 RHNO1 与 9-1-1 检查点钳和 TopBP1 相互作用，激活 ATR/Chk1 信号通路，这是 DRS 反应的关键介质。此外，RHNO1 最近还被确定为 theta 介导的末端连接 (TMEJ) 的关键促进剂，这是一种与癌症进展和化疗耐药有关的 DNA 修复机制。在这篇文献综述中，我们概述了我们目前对 RHNO1 的理解，包括其结构、在 DRS 反应中的功能以及在 DNA 修复中的作用，并讨论了其作为癌症治疗靶点的潜力。 RHNO1 的治疗靶向有望治疗 DRS 升高的肿瘤以及 DNA 修复缺陷的肿瘤，包括同源重组 DNA 修复缺陷 (HRD) 肿瘤。对 RHNO1 在癌症中的功能的进一步研究以及针对 RHNO1 的方法的开发预计将产生癌症治疗的新策略。© 2024。作者获得 Springer Nature Limited 的独家许可。

The DNA replication stress (DRS) response is a crucial homeostatic mechanism for maintaining genome integrity in the face of intrinsic and extrinsic barriers to DNA replication. Importantly, DRS is often significantly increased in tumor cells, making tumors dependent on the cellular DRS response for growth and survival. Rad9-Hus1-Rad1 Interacting Nuclear Orphan 1 (RHNO1), a protein involved in the DRS response, has recently emerged as a potential therapeutic target in cancer. RHNO1 interacts with the 9-1-1 checkpoint clamp and TopBP1 to activate the ATR/Chk1 signaling pathway, the crucial mediator of the DRS response. Moreover, RHNO1 was also recently identified as a key facilitator of theta-mediated end joining (TMEJ), a DNA repair mechanism implicated in cancer progression and chemoresistance. In this literature review, we provide an overview of our current understanding of RHNO1, including its structure, function in the DRS response, and role in DNA repair, and discuss its potential as a cancer therapeutic target. Therapeutic targeting of RHNO1 holds promise for tumors with elevated DRS as well as tumors with DNA repair deficiencies, including homologous recombination DNA repair deficient (HRD) tumors. Further investigation into RHNO1 function in cancer, and development of approaches to target RHNO1, are expected to yield novel strategies for cancer treatment.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.