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作 者:姚德山 张振刚[1] 龚开政[1] YAO De-shan;ZHANG Zhen-gang;GONG Kai-zheng(Department of Cardiology,The Affiliated Hospital of Yangzhou University,Yangzhou 225001,China)
出 处:《中国病理生理杂志》2020年第4期741-746,共6页Chinese Journal of Pathophysiology
基 金:国家自然科学基金资助项目(No.81470381;No.81770262);江苏省重点研发计划社会发展项目资助(No.BE2015663)。
摘 要:生物体细胞基因组完整性受到诸多因素的威胁,包括DNA复制过程中DNA碱基错配、化学物质产生的碱基加合物(adduct formation)和交叉链(cross-links)、紫外线诱导的碱基损伤、电离辐射导致的DNA单链或双链断裂等。DNA双链断裂(DNAdouble-strand break,DSB)被认为是细胞毒性最强的DNA损伤。DNA damage presents a major threat to genome stability. Repairing damaged DNA is essential for maintaining genome integrity and preventing genome instability-related diseases,such as cancer. DNA damage response is a multicomplex network of signaling pathways involved in DNA damage repair,cell cycle checkpoints and apoptosis,which mediates the cellular response to endogenous and exogenous stresses. DNA double-strand break is the most serious form of DNA damage. Three members of the phosphatidylinositol 3-kinase(PI3K)-related kinase(PIKK)protein family,DNA-PK,ATM and ATR,are key effectors of DNA damage response and are extensively linked to tumourigenesis and survival of cancer cells after radio-/chemotherapy. This article mainly discusses their functions,and mechanisms of activation and regulation.
关 键 词:DNA损伤反应 DNA双链断裂 DNA依赖性蛋白激酶 ATM蛋白 ATR蛋白
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