DeWitt Jerry Tyler, Raghunathan Megha, Haricharan Svasti
Department of Biology, San Diego State University, San Diego, CA, USA; Cancer Biology and Signaling Program, UCSD Moores Cancer Center, San Diego, CA, USA.
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Trends Cancer. 2025 Jan;11(1):49-61. doi: 10.1016/j.trecan.2024.10.001. Epub 2024 Oct 28.
DNA damage repair (DDR) proteins are well recognized as guardians of the genome that are frequently lost during malignant transformation of normal cells across cancer types. To date, their tumor suppressor functions have been generally regarded as a consequence of their roles in maintaining genomic stability: more genomic instability increases the risk of oncogenic transformation events. However, recent discoveries centering around DNA mismatch repair (MMR) proteins suggest a broader impact of the loss of DDR proteins on cellular processes beyond genomic instability. Here, we explore the clinical implications of nonrepair roles for DDR proteins, using the growing evidence supporting roles for DNA MMR proteins in cell cycle and apoptosis regulation, metabolic function, the cellular secretome, and immunomodulation.
DNA损伤修复（DDR）蛋白被公认为基因组的守护者，在各类癌症中正常细胞发生恶性转化的过程中，它们常常缺失。迄今为止，其肿瘤抑制功能通常被认为是它们在维持基因组稳定性方面发挥作用的结果：更多的基因组不稳定性会增加致癌转化事件的风险。然而，最近围绕DNA错配修复（MMR）蛋白的发现表明，DDR蛋白缺失对细胞过程的影响比基因组不稳定性更为广泛。在此，我们利用越来越多的证据来探讨DDR蛋白非修复作用的临床意义，这些证据支持DNA MMR蛋白在细胞周期和凋亡调控、代谢功能、细胞分泌组以及免疫调节中发挥作用。
