Jerry Tyler DeWitt, Megha Raghunathan, Svasti Haricharan
{"title":"Nonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology.","authors":"Jerry Tyler DeWitt, Megha Raghunathan, Svasti Haricharan","doi":"10.1016/j.trecan.2024.10.001","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":null,"pages":null},"PeriodicalIF":14.3000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.trecan.2024.10.001","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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，在正常细胞向各种癌症类型恶性转化的过程中，它们经常丢失。迄今为止，人们普遍认为它们的抑瘤功能是维持基因组稳定性的结果：基因组越不稳定，致癌转化的风险就越大。然而，最近围绕 DNA 错配修复（MMR）蛋白的发现表明，除基因组不稳定性外，DDR 蛋白的缺失还会对细胞过程产生更广泛的影响。在这里，我们利用越来越多的证据支持 DNA MMR 蛋白在细胞周期和凋亡调节、代谢功能、细胞分泌组和免疫调节中的作用，探讨 DDR 蛋白的非修复作用对临床的影响。
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Trends in Cancer, a part of the Trends review journals, delivers concise and engaging expert commentary on key research topics and cutting-edge advances in cancer discovery and medicine.
Trends in Cancer serves as a unique platform for multidisciplinary information, fostering discussion and education for scientists, clinicians, policy makers, and patients & advocates.Covering various aspects, it presents opportunities, challenges, and impacts of basic, translational, and clinical findings, industry R&D, technology, innovation, ethics, and cancer policy and funding in an authoritative yet reader-friendly format.
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