Kohnken Rebecca, Kodigepalli Karthik M, Wu Li
Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH, 43210, USA.
Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, 43210, USA.
Mol Cancer. 2015 Sep 29;14:176. doi: 10.1186/s12943-015-0446-6.
Regulation of intracellular deoxynucleoside triphosphate (dNTP) pool is critical to genomic stability and cancer development. Imbalanced dNTP pools can lead to enhanced mutagenesis and cell proliferation resulting in cancer development. Therapeutic agents that target dNTP synthesis and metabolism are commonly used in treatment of several types of cancer. Despite several studies, the molecular mechanisms that regulate the intracellular dNTP levels and maintain their homeostasis are not completely understood. The discovery of SAMHD1 as the first mammalian dNTP triphosphohydrolase provided new insight into the mechanisms of dNTP regulation. SAMHD1 maintains the homeostatic dNTP levels that regulate DNA replication and damage repair. Recent progress indicates that gene mutations and epigenetic mechanisms lead to downregulation of SAMHD1 activity or expression in multiple cancers. Impaired SAMHD1 function can cause increased dNTP pool resulting in genomic instability and cell-cycle progression, thereby facilitating cancer cell proliferation. This review summarizes the latest advances in understanding the importance of dNTP metabolism in cancer development and the novel function of SAMHD1 in regulating this process.
细胞内脱氧核苷三磷酸（dNTP）池的调节对基因组稳定性和癌症发展至关重要。dNTP池失衡会导致诱变增强和细胞增殖，从而引发癌症。靶向dNTP合成和代谢的治疗药物常用于治疗多种类型的癌症。尽管有多项研究，但调节细胞内dNTP水平并维持其稳态的分子机制仍未完全阐明。SAMHD1作为首个哺乳动物dNTP三磷酸水解酶的发现，为dNTP调节机制提供了新的见解。SAMHD1维持调节DNA复制和损伤修复的稳态dNTP水平。最近的进展表明，基因突变和表观遗传机制导致多种癌症中SAMHD1活性或表达下调。SAMHD1功能受损会导致dNTP池增加，从而导致基因组不稳定和细胞周期进程，进而促进癌细胞增殖。本综述总结了在理解dNTP代谢在癌症发展中的重要性以及SAMHD1在调节这一过程中的新功能方面的最新进展。
