WCSS Team Unlocks a Novel Mechanism Supporting DNA Repair
Researchers from West China School of Stomatology (WCSS), Sichuan University have discovered that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.
Innate immunity provides the first line of defense against invading pathogens and plays an important role in the homeostasis of oral mucosa. Cyclic cGMP-AMP synthase (cGAS) is a well-established DNA sensor in innate immune responses. Nevertheless, how the innate immune machinery regulates metabolic enzymes to facilitate DNA repair is still largely unknown.
In this study, researchers demonstrated that ATM phosphorylates PRPS1/2 S16 in response to ionizing radiation, which in turn causes PRPS1/2 T228 phosphorylation in a cGAS/STING-axis- and TBK1-dependent manner. T228 phosphorylation activates PRPS1/2 and promotes deoxyribonucleotide synthesis, thereby supporting DNA repair and cell viability.
Model of innate immune machinery-mediated PRPS1/2 activation and deoxyribonucleotide synthesis in response to ionizing radiation.
Their findings, published in the journal Cell Metabolism on 5 October 2021, highlight a novel and important mechanism underlying an innate immune response-guided deoxyribonucleotide metabolism supporting DNA repair, thus implying potential targets to prevent or alleviate ionizing radiation-induced DNA damages.
This study was conducted by Dr. Rui Liu’s team and Dr. Qianming Chen’s team. Dr. Rui Liu is the first author and lead contact. Dr. Qianming Chen is the co-corresponding author. Additional authors include Jingyi Li, Jichun Shao, Jong-Ho Lee, Xuemei Qiu, Yanxuan Xiao, Bowen Zhang, Yilong Hao, Mi Li.
For more details of this study, please click the link below.
https://www.sciencedirect.com/science/article/pii/S1550413121003259?via%3Dihub#ack0010
