电离辐射诱导DNA损伤进而引起自噬的发生。脱氧胞苷激酶（dCK）是磷酸化天然脱氧核糖核苷酸以及外源性抗肿瘤、抗病毒的核苷类似物药物的关键酶，在DNA合成及药物活化方面起关键作用。dCK在放射生物学领域少有报道。我们发现，dCK参与电离辐射诱导DNA损伤和自噬。本项目拟就dCK如何调控电离辐射诱导的自噬开展探索：（1）验证dCK参与辐射诱导自噬的调控；（2）确定ATM磷酸化dCK Ser74为辐射诱导自噬所必需；（3）确定dCK-AKT-mTOR通路的调控作用；（4） 确定HSP90-dCK-AKT-NFkB- BECLIN通路的调控作用；（5）确定dCK的LIR（LC3 interacting region）结构域结合LC3调控自噬。本研究将为辐射诱导自噬的调控机制提供新的理论基础，鉴于dCK在辐射诱导的DNA损伤中变化显著，可作辐射剂量计，以dCK为靶点对于辐射防护有重要的意义。

Ionozing radiation could induce DNA damage and autophagy. Deoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage and is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. The roles of dCK in drugs metabolism is a wide concern, while its application in radiobiological regulation is still unclear. We have found that dCK functions in the processes of DNA damage and radiation-induced autophagy. In this study we are aiming to elucidate the roles of dCK in radiation-induced autophagy and the underlying mechanisms. Five parts will be included: (1) to validate the fact that dCK participates in the radiation-induced autophagy; (2) to verify that the phosphorylation of dCK-Ser 74 by ATM is required for the radiation-induced autophagy;(3) to confirm the regulatory roles of dCK-AKT-mTOR pathway; (4) to confirm the regulatory roles of HSP90-dCK-AKT-IKK-NFkB- BECLIN pathway; (5) to elucidate if dCK interacts with MAPLC3 via its LIR （LC3-interacting region）domain and consequently regulate the process of autophagy. This study will provide a new insight and molecular mechanisms for radiobiology theory. In addition, based on the facts that dCK could change the radiosensitivity and DNA damage could alter dCK expression and activity, dCK could be used as a biological dosimeter and a target for both radiotherapy and radiation protection.