Department of Cellular and Molecular Medicine and University of Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ, 85724, United States.
Department of Cellular and Molecular Medicine and University of Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ, 85724, United States.
DNA Repair (Amst). 2020 Sep;93:102920. doi: 10.1016/j.dnarep.2020.102920.
Efficient DNA repair is essential to maintain genomic integrity. An average of 30,000 base lesions per cell are removed daily by the DNA glycosylases of the base excision repair machinery. With the advent of whole genome sequencing, many germline mutations in these DNA glycosylases have been identified and associated with various diseases, including cancer. In this graphical review, we discuss the function of the NTHL1 DNA glycosylase and how genomic mutations and altered function of this protein contributes to cancer and aging. We highlight its role in a rare tumor syndrome, NTHL1-associated polyposis (NAP), and summarize various other polymorphisms in NTHL1 that can induce early hallmarks of cancer, including genomic instability and cellular transformation.
有效的 DNA 修复对于维持基因组完整性至关重要。碱基切除修复机制中的 DNA 糖苷酶每天平均清除 30000 个碱基损伤。随着全基因组测序的出现，已经鉴定出这些 DNA 糖苷酶中的许多种系突变，并与包括癌症在内的各种疾病相关。在这篇图文综述中，我们讨论了 NTHL1 DNA 糖苷酶的功能，以及该蛋白的基因组突变和功能改变如何导致癌症和衰老。我们强调了它在一种罕见的肿瘤综合征 NTHL1 相关息肉病 (NAP) 中的作用，并总结了 NTHL1 中可以诱导包括基因组不稳定性和细胞转化在内的癌症早期标志的各种其他多态性。
