DSB修复蛋白ATM DNA-PKcs与肿瘤放射敏感性关系的研究进展  

Progress of Studies on the Relationship of ATM and DNA-PKcs with Tumor Radiosensitivity

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作  者:冯济龙[1] 黄立新[1] 王力军[1] 

机构地区:[1]沈阳市第五人民医院放疗科,沈阳市110023

出  处:《中国肿瘤临床》2011年第16期985-987,共3页Chinese Journal of Clinical Oncology

摘  要:放射线主要通过导致细胞DNA双链断裂(DSB)而起到杀死肿瘤细胞的作用,但细胞都有不同程度的DSB修复能力,研究证实DSB修复水平与细胞放射敏感性关系密切。在人类细胞内有2种DSB修复途径:一种是以DNA依赖蛋白激酶(DNA-PK)复合物为主的非同源末端连接(NHEJ)修复,另一种是以毛细血管扩张性共济失调症突变蛋白(ATM)为主的同源重组(HR)修复在人体内,NHEJ修复是最主要的修复途径,DNA依赖蛋白激酶催化亚单位(DNA-PKcs)是DNA-PK复合物的主要功能单位。DNA-PKcs的激酶活性是NHEJ修复所必须的,其在DSB修复中起核心作用近年来的研究显示ATM、DNA-PKcs蛋白表达水平与肿瘤放射敏感性有关。该综述将有关ATM、DNA-PKcs的功能、在肿瘤组织中的表达及与肿瘤放射敏感性关系的研究进行简要回顾。Radiation kills tumor cells mainly via DNA double-strand breaks ( DSBs ). However, tumor cells have different levels of DSB-repairing capacity. The level of DSB repair is related to the cell radiosensitivity. In human cells, there are two DSB repair pathways. The first is non-homologous end joining ( NHEJ ), which is based on DNA-dependent protein kinases ( DNA-PKs ). The second is homologous recombination repair ( HR ), which is based on ataxia telangiectasia mutated ( ATM ). In humans, NHEJ is the main re- pair pathway. DNA-PK catalytic subunits ( DNA-PKcs ) are the primary functional units of DNA-PKs. The activities of DNA-PKcs are necessary for NHEJ and DSB repair. Studies on the structures and functions of ATM and DNA-PKcs, on their expression levels in tu- mor cells, as well as on tumor radiosensitivity are increasing. The expression levels of ATM and DNA-PKcs are found to be related to the cell radiosensitivity. This article reviews the studies on the functions and expression of these two proteins in tumor cells, and their relationships with cell radiosensitivity.

关 键 词:DNA双链断裂 ATM DNA—PKcs 放射敏感性 肿瘤治疗 

分 类 号:R730.55[医药卫生—肿瘤]

 

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