DNA损伤修复反应的双刃剑效应在肿瘤与衰老发生发展中的作用  

DNA Damage:A Double-edge Sword in Tumor and Cellular Senescence

作　　者：李小曼[1] 徐红德[1] 蔺美娜[1] 宋晓宇[1] 冯艳玲[1] 羿菲[1] 刘爽[1] 曹流[1] 

机构地区：[1]中国医科大学转化医学研究所教育部医学细胞生物学重点实验室,沈阳110001

出　　处：《中国细胞生物学学报》2013年第2期134-140,共7页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81130042;31171323);辽宁省高等学校创新团队支持计划(批准号:LT2011011)资助的课题~~

摘　　要：人类生存环境中的有害物质、机体正常代谢产生的氧化自由基、端粒缩短或端粒酶活性改变、原癌基因激活或抑癌基因失活等均可造成DNA损伤。通过启动DNA损伤修复反应,激活p53/p21或p16/Rb信号转导途径可以引发细胞周期阻滞,为修复破损的DNA赢得时间,避免不完整的DNA信息继续传递下去。过度的细胞周期阻滞将引起不可逆的细胞增殖停滞并最终引起细胞衰老,而当损伤的DNA没有完全修复就无限制的进入细胞周期时,将会诱发肿瘤的形成。肿瘤和衰老的发生机制是相互对立、相互交织的,而DNA损伤修复反应是联系二者的纽带。Both exogenous and endogenous insults can result in DNA damage, which can be readily sensed by DNA repair machinery, and consequently trigger a series of cellular events, namely ＂DNA Damage Response＂ （DDR）, to achieve cell cycle arrest. Transient cell cycle arrest will allow DNA repair and prevent the passing of aberrant DNA to the daughter cells. However, persistent DNA damage could result in irreversible cell proliferation arrest （senescence） to terminate cell function, or programmed cell death （apoptosis） to eliminate impaired cells.Under circumstances of excessive accumulation of incompletely or inaccurately repaired DNA and hence gathering of oncogenic mutations, cells may acquire unrestrictedly proliferative properties and propagate into cancer. Despite the fact that cancer and senescence are oppositely characterized by hyperproliferation and hypoproliferation, respectively, they are not mutually exclusive and actually driven by a unified mechanism： DNA damage.

关 键 词：DNA损伤修复反应 细胞周期阻滞 凋亡 肿瘤 衰老 

分 类 号：R730.5[医药卫生—肿瘤]