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许多内源性和外源性的损伤因素均能导致DNA损伤,如活性氧、紫外线辐射、电离辐射、化学致癌药物及烷化剂等。哺乳动物细胞对于致DNA损伤因素的各种刺激会产生一系列应答反应,如细胞周期抑制、DNA修复、DNA去甲基化、细胞生存和细胞凋亡等。生长抑制DNA损伤基因45(Gadd45)在DNA损伤诱导的细胞应答反应中发挥重要作用。细胞内、外环境的多种因素在转录水平、翻译后水平等多个层次对Gadd45进行精确调节。Gadd45家族蛋白与年龄相关疾病、寿命及老化相关。
Many endogenous and exogenous damage factors can cause DNA damage such as reactive oxygen species, ultraviolet radiation, ionizing radiation, chemical carcinogens and alkylating agents. Mammalian cells produce a variety of response to various stimuli that cause DNA damage, such as cell cycle inhibition, DNA repair, DNA demethylation, cell survival and apoptosis. Growth Inhibitory DNA Damage Gene 45 (Gadd45) plays an Important Role in DNA Damage-Induced Cellular Responses. Many factors of intracellular and extracellular environment regulate Gadd45 accurately at multiple levels, such as transcriptional level and posttranslational level. The Gadd45 family of proteins is associated with age-related disease, longevity and aging.