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人NFBD1启动子区域顺式作用元件CHR的定点突变分析 被引量：1

Site-directed mutagenesis of cis-acting element,CHR,in human NFBD1 promoter region
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摘要 目的对NFBD1启动子区域顺式作用元件CHR进行定点突变分析,以分析CHR在NFBD1转录调控中的作用。方法以原有NFBD1核心启动子荧光素酶报告基因重组体NFBD1-PS1-325为模板,采用PCR介导的基因定点突变技术对NFBD1启动子区域中的CHR位点进行定点突变,构建相应的CHR定点突变重组体;采用荧光素酶双报告基因分析技术检测各重组体的启动子活性,分析CHR定点突变对NFBD1启动子活性的影响;结合阿霉素处理,分析CHR在DNA损伤后NFBD1转录下调中的潜在作用。结果CHR定点突变后能显著降低NFBD1的启动子活性;CHR定点突变后显著减弱了DNA损伤后NFBD1的转录下调比例。结论CHR参与NFBD1的基础转录调控及DNA损伤后的转录下调。 Objective To investigate the role of a cis-acting element,cell cycle genes homology region （CHR）,in the transcriptional regulation of human NFBD1 gene （a nuclear factor with BRCT domain 1） by conducting a site-directed mutagenesis analysis on the element in human NFBD1 promoter region.Methods Wild type of NFBD1 promoter reporter,NFBD1-PS1-325,was used as template to make CHR mutant by using PCR based site-directed mutagenesis.Dual luciferase reporter assay was used to determine promoter reporter activity.Adiamycin treatment was employed to investigate the role of CHR in the transcriptional downregulation of NFBD1 after DNA damage.Results Site-directed mutagenesis of CHR caused a significant decrease in NFBD1 promoter activity,and also attenuated the transcriptional down-regulation of NFBD1 after DNA damage.Conclusion CHR element might be involved in both basic transcriptional regulation and transcriptional downregulation of NFBD1 after DNA damage.
作者 朱江 兰欢 洪苏玲 卜友泉
机构地区 重庆医科大学附属第一医院耳鼻咽喉科 重庆医科大学附属第一医院分子医学与肿瘤研究中心
出处 《第三军医大学学报》 CAS CSCD 北大核心 2010年第10期1020-1023,共4页 Journal of Third Military Medical University
基金 国家自然科学基金(30801356) 重庆市教委科学技术研究项目(KJ090305) 重庆市卫生局课题(07-2-026)~~
关键词 NFBD1 启动子 转录调控 CHR 顺式作用元件 a nuclear factor with BRCT domain 1 Promoter transcriptional regulation cell cycle genes homology region cis-acting element
分类号 R394-33 [医药卫生—医学遗传学] R394.3 [医药卫生—医学遗传学]
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参考文献20

  • 1Stucki M, Jackson S P. MDC1/NFBD1 : a key regulator of the DNA damage response in higher enkaryotes [J]. DNA Repair (Amst), 2004, 3 (8/9) : 953 - 957.
  • 2Ozaki T, Nagase T, Ichimiya S, et al. NFBD1/KIAAO170 is a novel nuclear transcriptional transactivator with BRCT domain[J]. DNA Cell Biol, 2000, 19(8) : 475 -485.
  • 3Lou Z, Minter-Dykhouse K, Franco S, et al. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals[J]. Mol Cell, 2006, 21 (2) : 187 -200.
  • 4Stewart G S, Wang B, Bignell C R, et al. MDC1 is a mediator of the mammalian DNA damage checkpoint [ J ]. Nature, 2003, 421 (6926) : 961 - 966.
  • 5Goldberg M, Stucki M, Falck J, et al. MDC1 is required for the intra-S-phase DNA damage checkpoint [ J ]. Nature, 2003, 421 (6926) : 952 - 956.
  • 6Lou Z, Minter-Dykhouse K, Wu X, et al. MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways[J]. Nature, 2003, 421 (6926) : 957 -961.
  • 7Coster G, Hayouka Z, Argaman L, et al. The DNA damage response mediator MDC1 directly interacts with the anaphase-promoting complex/cyclosome[J]. J Biol Chem, 2007, 282 (44) : 32053 - 32064.
  • 8Rai R, Phadnis A, Haralkar S, et al. Differential regulation of centrosome integrity by DNA damage response proteins [ J ]. Cell Cycle, 2008, 7(14) : 2225 -2233.
  • 9Eliezer Y, Argaman L, Rhie A, et al. The direct interaction between 53BP1 and MDC1 is required for the recruitment of 53BP1 to sites of damage[J]. J Biol Chem, 2009, 284 (1): 426-435.
  • 10Townsend K, Mason H, Blackford A N, et al. Mediator of DNA damage checkpoint 1 ( MDC1 ) regulates mitotic progression [ J ]. J Biol Chem, 2009, 284(49): 33939-33948.

二级参考文献48

  • 1卜友泉,罗绪刚,刘彬,李素芬.一步3′RACE快速构建鸡MnSOD全长cDNA克隆[J].遗传,2004,26(4):519-521. 被引量：1
  • 2Stucki M, Jackson S P. MDC1/NFBD1: a key regulator of the DNA damage response in higher eukaryotes [ J ]. DNA Repair (Amst), 2004, 3(8-9) :953-957
  • 3Lou Z, Minter-Dykhouse K, Franco S, et al. MDC1 maintains genomic stability by participating in the amplification of ATM- dependent DNA damage signals [J]. Mol Cell, 2006, 21(2):187- 20O
  • 4Nagase T, Seki N, lshikawa K A, et al. Prediction of the coding sequences of unidentified human genes V: The ceding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of eDNA clones from human cell line KG-1[J]. DNA Res, 1996, 3( 1 ) : 17-24
  • 5Ozaki T, Nagase T, Ichiariya S, et al. NFBD1/KIAA0170 is a novel nuclear transcriptional transactivator with BRCT domain [J]. DNA Cell Biol, 2000, 19(8):475-485
  • 6Stewart G S, Wang B, Bignell C R, et al. MDC1 is a mediator of the mammalian DNA damage checkpoint [ J]. Nature, 2003, 421 (6926) : 961-966
  • 7Goldberg M, Stucki M, Falck J, et al. MDC1 is required for the intra-S-phase DNA damage checkpoint [J]. Nature, 2003, 421 (6926) : 952-956
  • 8Lou Z, Minter-Dykhouse K, Wu X, et al. MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways [J]. Nature, 2003, 421(6926) :957-961
  • 9Stucki M, Clapperton J A, Mohammad D, et al. MDCI directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks [J]. Cell, 2005, 123(7):1213-1226
  • 10Zhang J, Ma Z, Treszezamsky A, et al. MDC1 interacts with Rad51 and facilitates homologous recombination [ J]. Nat Struct Mol Biol, 2005, 12(10) :902-909

共引文献15

同被引文献20

  • 1周赞虎,张永祥,陈枝华,刘仁海,田蕴,郑天凌.基因改造中快速PCR定点突变方法应用[J].中国公共卫生,2007,23(1):102-103. 被引量：5
  • 2Seeger C,Mason W S. Hepatitis B virus biology[J].Microbiology and Molecular Biology Reviews,2000,(01):51-68.
  • 3Bouchard M J,Schneider R J. The enigmatic X gene of hepatitis B virus[J].Journal of Virology,2004,(23):12725-12734.
  • 4Levrero M,Pollicino T,Petersen J. Control of cccDNA function in hepatitis B virus infection[J].Journal of Hepatology,2009,(03):581-592.doi:10.2169/internalmedicine.48.1469.
  • 5Ryu D K,Ahn B Y,Ryu W S. Proximity between the cap and 5'epsilon stem-loop structure is critical for the suppression of pgRNA translation by the hepatitis B viral polymerase[J].Virology,2010,(01):56-64.doi:10.1016/j.virol.2010.07.005.
  • 6Lucifora J,Arzberger S,Durantel D. Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection[J].Journal of Hepatology,2011,(05):996-1003.doi:10.1016/j.jhep.2011.02.015.
  • 7Gong Q,Chen S,Guo J. Chromosome remodeling related to hepatitis B virus replication in HepG2 cells[J].Dna and Cell Biology,2011,(06):347-354.doi:10.1089/dna.2010.1172.
  • 8Tang H,Delgermaa L,Huang F. The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication[J].Journal of Virology,2005,(09):5548-5556.
  • 9Keasler V V,Hodgson A J,Madden C R. Enhancement of hepatitis B virus replication by the regulatory X protein in vitro and in vivo[J].Journal of Virology,2007,(06):2656-2662.
  • 10Pollicino T,Belloni L,Raffa G. Hepatitis B virus replication is regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 histones[J].Gastroenterology,2006,(03):823-837.doi:10.1053/j.gastro.2006.01.001.

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第三军医大学学报
2010年 第10期

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