DNA repair and synthetic lethality  

作　　者：Gong-she Guo Feng-mei Zhang Rui-jie Gao Robert Delsite Zhi-hui Feng Simon N. Powell 

机构地区：[1]School of Public Health, Shandong University, Jinan 250012, China [2]Second People＇s Hospital of Weifang, Weifang 261041, China [3]Department of Radiation Oncology, Washington University in St Louis, St Louis MO 63108, USA [4]Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York NY10065, USA

出　　处：《International Journal of Oral Science》2011年第4期176-179,共4页国际口腔科学杂志（英文版）

基　　金：US Public Health Service Grants (Grant No. CA107640, to SNP);"Independent Innovation Foundation of Shandong University IIFSDU" (Grant No. 2010 TB017, to ZF);the National Natural Science Foundation of China (Grant No.81172527, to ZF and SNP) for financial support

摘　　要：Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination （HR）, are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly （adenosine diphosphate （ADP）-ribose） polymerase （PARP） inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination （HR）, are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly （adenosine diphosphate （ADP）-ribose） polymerase （PARP） inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.

关 键 词：DNA repair homologous recombination synthetic lethality BRCA Rad52 

分 类 号：Q523[生物学—生物化学] TQ464.9[化学工程—制药化工]