内质网在蛋白质合成和分泌、钙离子稳态调控以及脂质合成等重要细胞生理过程中发挥关键作用。在形态上,内质网可分为管状和片层状二种类型，它们的形成和维持受内质网形态塑造蛋白、细胞骨架等多种因子调控。但是对于不同生理条件或者环境因素刺激下内质网形态变化的机制尚不清楚。DNA损伤应答对细胞和个体存活至关重要。我们初步结果表明，在诱导DNA损伤后，内质网形态发生剧烈变化，并且该过程可能通过p53下游蛋白EI24介导。在本项目中，我们将研究DNA损伤与内质网形态变化之间的相关性，深入研究EI24调控DNA损伤诱导的内质网变化的机制，同时进一步寻找其它在DNA损伤条件下参与调控内质网形态变化的蛋白，探讨DNA损伤调控内质网形态变化的分子机制。此外，还将阐明DNA损伤后内质网形态变化的生理功能。本项目的实施将揭示DNA损伤诱导内质网形态动态变化过程、调控机制及其生理意义，为相关疾病防治提供理论依据。

The endoplasmic reticulum (ER) plays important roles in various physiological processes such as protein synthesis and secretion, calcium homeostasis and lipid metabolism. Morphologically, the ER is divided into perinuclear sheets and a tubular network to exert different functions. However, it’s largely unknown how the ER morphology is regulated under different physiological conditions or environmental stress. Proper response to DNA damage is necessary for the survival of cell and individuals. Our preliminary data show that under DNA-damaging conditions, the ER morphology changes dramatically, which may possibly be mediated by EI24, a p53 downstream protein. In this project, we will investigate how DNA damage regulates ER morphology, the role of EI24 in this process, as well as search for other potential regulators, so as to reveal the molecular mechanism of DNA-damage-induced ER morphological change. Moreover, we will also study the function of ER morphological change following DNA damage. This project will uncover the dynamic regulation of ER morphology under DNA damage and its physiological significance, which will also provide theoretical support for related diseases.