《生命科学》 2021, 33(6): 696-701

Gadd45α在干细胞DNA损伤中的作用

宋　涛 , 单春华^*

东北林业大学生命科学学院，哈尔滨 150040

摘　要：

基因组完整性对于细胞和组织功能至关重要，这种稳态会不断地受到内源性和外源性应激刺激的影响。干细胞对这些应激刺激十分敏感，其DNA 会发生不同程度的损伤，诱导干细胞内固有的DNA 修复机制。组织特异性干细胞是局部环境中的多能群体，在其整个生命过程中负责维持组织或者系统的完整性。组织特异性干细胞在受到应激刺激之后，能通过某些反应修复损伤或激活程序性凋亡，从而减少由DNA损伤导致潜在的突变。生长停滞和DNA 损伤诱导蛋白45α (growth arrest and DNA damage-45 alpha, Gadd45α)是细胞周期调控因子和生长抑制因子，其表达受到多种因素的调节，参与多种细胞DNA 损伤反应。Gadd45α 蛋白在组织特异性干细胞DNA 损伤中发挥重要的作用。Gadd45α 蛋白通过结合其他相关蛋白质控制细胞周期检测点、参与DNA 修复和调控信号转导，是维持基因组稳定性的重要组成部分。该文综述了Gadd45α 在胚胎干细胞、神经干细胞、造血干细胞、肠干细胞等干细胞DNA 损伤中的作用以及涉及的信号通路，为进一步探讨Gadd45α 在细胞中潜在的作用以及利用Gadd45α 进行疾病治疗提供理论依据。

通讯作者：单春华 , Email:chhshan@sina.com

The role of Gadd45α in stem cell DNA damage

SONG Tao , SHAN Chun-Hua^*

College of Life Science, Northeast Forestry University, Harbin 150040, China

Abstract:

Genome integrity is essential for cellular and tissue function, and this homeostasis is constantly affected by endogenous and exogenous stress stimuli. Stem cells are sensitive to these stress stimuli, and their DNA is subject to varying degrees of damage, which induces the inherent DNA repair mechanism in stem cells. Tissue-specific stem cells are multipotent populations in a localized environment and are responsible for maintaining the integrity of the tissues or systems throughout their life cycle. Tissue-specific stem cells can repair damage or activate programmed apoptosis to reduce potential mutations caused by DNA damage after being stimulated by stress. Growth arrest and DNA damage-45 alpha (Gadd45α) is a cell cycle regulator and growth inhibitor whose expression is regulated by a variety of factors and is involved in many cellular DNA damage responses. Gadd45α plays an important role in tissue-specific stem cell DNA damage. Gadd45α controls cell cycle checkpoints, participates in DNA repair and regulates signal transduction by combining with other related proteins, and is a component in maintaining genome stability. This article reviewed the role of Gadd45α in DNA damage of stem cells such as embryonic stem cells, neural stem cells, hematopoietic stem cells, intestinal stem cells and other stem cells as well as the signaling pathways involved, providing a theoretical basis for further exploring the potential role of Gadd45α in cells and its application in disease treatment.

Communication Author：SHAN Chun-Hua , Email:chhshan@sina.com