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Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

文献类型：期刊论文

作者Li, Weiwei2; Wang, Jufang1; Zhang, Yingmei2; Qi, Yongmei2; Ding, Nan1; Kong, Jinxin2; Zhang, Xiaoning2; Gu, Xueyan2; Huang, Dejun2
刊名MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
出版日期2015-09-01
卷号779页码:112-123
关键词Heavy metal cadmium (Cd) DNA damage repair (DDR) Non-homologous end joining (NHEJ) DNA-dependent protein kinase X-ray cross-complementing protein 4 DNA Ligase IV
ISSN号0027-5107
DOI10.1016/j.mrfmmm.2015.07.002
英文摘要Although studies have shown that cadmium (Cd) interfered with DNA damage repair (DDR), whether Cd could affect non-homologous end joining (NHEJ) repair remains elusive. To further understand the effect of Cd on DDR, we used X-ray irradiation of Hela cells as an in vitro model system, along with gamma H2AX and 53BP1 as markers for DNA damage. Results showed that X-ray significantly increased gamma H2AX and 53BP1 foci in Hela cells (p<0.01), all of which are characteristic of accrued DNA damage. The number of foci declined rapidly over time (1-8 h postirradiation), indicating an initiation of NHEJ process. However, the disappearance of gamma H2AX and 53BP1 foci was remarkably slowed by Cd pretreatment (p<0.01), suggesting that Cd reduced the efficiency of NHEJ. To further elucidate the mechanisms of Cd toxicity, several markers of NHEJ pathway including Ku70, DNA-PKcs, XRCC4 and Ligase IV were examined. Our data showed that Cd altered the phosphorylation of DNA-PKcs, and reduced the expression of both XRCC4 and Ligase IV in irradiated cells. These observations are indicative of the impairment of NHEJ-dependent DNA repair pathways. In addition, zinc (Zn) mitigated the effects of Cd on NHEJ, suggesting that the Cd-induced NHEJ alteration may partly result from the displacement of Zn or from an interference with the normal function of Zn-containing proteins by Cd. Our findings provide a new insight into the toxicity of Cd on NHEJ repair and its underlying mechanisms in human cells. (C) 2015 Elsevier B.V. All rights reserved.
WOS关键词DOUBLE-STRAND BREAKS ; CELL-PROLIFERATION ; HOMOLOGOUS RECOMBINATION ; METAL-IONS ; EXPOSURE ; PROTEINS ; CANCER ; DAMAGE ; ZINC ; CARCINOGENESIS
资助项目National Natural Science Foundation of China[20907019] ; Fundamental Research Funds for the Central Universities[Lzujbky-2013-m03]
WOS研究方向Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
语种英语
WOS记录号WOS:000361251500012
出版者ELSEVIER SCIENCE BV
资助机构National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities
源URL[http://119.78.100.186/handle/113462/40714]  
专题近代物理研究所_生物物理研究室
通讯作者Huang, Dejun
作者单位1.Chinese Acad Sci, Inst Modern Phys, Gansu Key Lab Space Radiobiol, Lanzhou 730000, Peoples R China
2.Lanzhou Univ, Sch Life Sci, Gansu Key Lab Biomonitoring & Bioremediat Environ, Lanzhou 730000, Peoples R China
推荐引用方式
GB/T 7714		 Li, Weiwei,Wang, Jufang,Zhang, Yingmei,et al. Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV[J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS,2015,779:112-123.
APA Li, Weiwei.,Wang, Jufang.,Zhang, Yingmei.,Qi, Yongmei.,Ding, Nan.,...&Huang, Dejun.(2015).Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV.MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS,779,112-123.
MLA Li, Weiwei,et al."Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV".MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS 779(2015):112-123.

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来源：近代物理研究所

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