1,2,3,4-Diepoxybutane-induced DNA-protein cross-linking in human fibrosarcoma (HT1080) cells.
1,2,3,4-Diepoxybutane-induced DNA-protein cross-linking in human fibrosarcoma (HT1080) cells.
复制标题
DOI：
10.1021/pr3011974
复制
发表时间：
2013-05-03
影响因子：
4.4
通讯作者：
Tretyakova NY
中科院分区：
文献类型：
--
作者：
Gherezghiher TB;Ming X;Villalta PW;Campbell C;Tretyakova NY
1，2，3，4-二环氧丁烷（DEB）是1，3-丁二烯（BD）的主要致癌代谢物，BD是一种重要的工业和环境化学品，存在于城市空气和香烟烟雾中。DEB是一种具有遗传毒性的双亲电体，能够交联细胞生物分子以形成DNA-DNA和DNA-蛋白质交联（DPC）。在目前的工作中，基于质谱的蛋白质组学表征DEB介导的DNA-蛋白质交联在人纤维肉瘤（HT 1080）细胞。在DEB存在下，在与染色体DNA共价交联的蛋白质中发现了超过150种蛋白质，包括组蛋白、高迁移率族蛋白、转录因子、剪接因子和微管蛋白。大部分交联蛋白质是参与DNA结合、转录调控、细胞信号传导、DNA修复和DNA损伤反应的已知因子。总蛋白水解酶的HPLC-ESI+-MS/MS分析揭示了1-（S-半胱氨酰）-4-（关-7-基）-2，3-丁二醇缀合物的存在，证实了DEB在蛋白质内的半胱氨酸硫醇和DNA内的N-7鸟嘌呤位置之间形成DPC。然而，需要相对高浓度的DEB来实现显著的DPC形成，这表明与抗肿瘤氮芥和铂化合物相比，它是差的交联剂。
1,2,3,4-diepoxybutane (DEB) is the key carcinogenic metabolite of 1,3-butadiene (BD), an important industrial and environmental chemical present in urban air and in cigarette smoke. DEB is a genotoxic bis-electrophile capable of cross-linking cellular biomolecules to form DNA-DNA and DNA-protein cross-links (DPCs). In the present work, mass spectrometry-based proteomics was employed to characterize DEB-mediated DNA-protein cross-linking in human fibrosarcoma (HT1080) cells. Over 150 proteins including histones, high mobility group proteins, transcription factors, splicing factors, and tubulins were found among those covalently cross-linked to chromosomal DNA in the presence of DEB. A large portion of the cross-linked proteins are known factors involved in DNA binding, transcriptional regulation, cell signaling, DNA repair, and DNA damage response. HPLC-ESI+-MS/MS analysis of total proteolytic digests revealed the presence of 1-(S-cysteinyl)-4-(guan-7-yl)-2,3-butanediol conjugates, confirming that DEB forms DPCs between cysteine thiols within proteins and the N-7 guanine positions within DNA. However, relatively high concentrations of DEB were required to achieve significant DPC formation, indicating that it is a poor cross-linking agent as compared to antitumor nitrogen mustards and platinum compounds.
登录
查看更多内容
影响因子：
4.1
作者：
Loecken, Elisabeth M.;Guengerich, F. Peter
通讯作者：
Guengerich, F. Peter
抗肿瘤氮的DNA-蛋白交联的蛋白质组学分析。
影响因子：
4.1
作者：
Loeber, Rachel L.;Michaelson-Richie, Erin D.;Codreanu, Simona G.;Liebler, Daniel C.;Campbell, Colin R.;Tretyakova, Natalia Y.
通讯作者：
Tretyakova, Natalia Y.
HMGA2表现出DRP/AP位点的切割活性，并保护癌细胞在化学疗法期间免受DNA破坏诱导的细胞毒性。
影响因子：
14.9
作者：
Summer H;Li O;Bao Q;Zhan L;Peter S;Sathiyanathan P;Henderson D;Klonisch T;Goodman SD;Dröge P
通讯作者：
Dröge P
影响因子：
4.1
作者：
Shin, Nah-Young;Liu, Qinfeng;Liebler, Daniel C.
通讯作者：
Liebler, Daniel C.
影响因子：
4.8
作者：
Barker, S;Weinfeld, M;Murray, D
通讯作者：
Murray, D