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维基百科

末端脫氧核苷酸轉移酶

末端脫氧核苷酸轉移酶Terminal deoxynucleotidyl transferaseTdT、末端轉移酶),是一種特殊的DNA聚合酶,顯示出未成熟的、"前B","前T淋巴細胞"和"急性淋巴性白血病/淋巴瘤細胞"。"末端轉移酶"於"抗體基因重組時"加上N核苷酸(N-nucleotide)至V(D)J的外显子上,能夠形成連接多樣性(Junctional diversity)的現象。在人類中,末端轉移酶是由DNTT基因來編碼。 [1][2]

TdT不存在於"胎肝造血干细胞"上,而在胎兒期明顯的損害B細胞之連接多樣性。[3]

功能 编辑

"末端轉移酶"催化添加核苷酸至DNA分子的3'末端的反应。不像大多數的DNA聚合酶,它不需要一個模板。這種酶的優選底物是3'突出端,但它也可以添加"核苷酸"(nucleotides)至"鈍末端"(blunt end)或"凹陷的3'末端"(recessed 3' end)。是一種必要的辅因子,但是在"體外"反应条件下(in vitro)鎂(Mg)及錳(Mn)也可以起相同的作用。

使用 编辑

末端轉移酶在分子生物學中的應用。它可以被用來在快速擴增cDNA末端(RACE)中來添加"核苷酸"(nucleotide),然後可以用來作為在後續PCR的"引物"(primer)的模板。它也可以用於添加標記放射性同位素的核苷酸,例如在TUNEL检测(末端脫氧核苷酸轉移酶"dUTP缺口末端標記"(dUTP Nick End Labeling)),用於细胞凋亡的示範(其中的標記,在某種程度上,通過片段化DNA來進行)。也可用於治療"急性淋巴性白血病"診斷之"免疫熒光測定"(immuno-fluorescence)。[4]

免疫組織化學中,抗體TdT酶可用於顯示未成熟的T細胞和B細胞以及多能的"造血(Haematopoiesis)幹細胞"的存在,其具有抗原,而成熟的淋巴樣細胞總是呈"TdT陰性"。而末端轉移酶陽性的細胞中發現少量的健康淋巴結扁桃體,急性淋巴細胞白血病的惡性細胞也呈"TdT陽性",而抗體,因此可以被用來作為面板診斷及區別這種疾病的一部分,比如,"初發期的小細胞腫瘤"(small cell tumours of childhood)。[5]

參見 编辑

  • DNA
  • DNA聚合酶
  • 先天性無子宮無陰道症候群(Müllerian agenesis/MRKH)

註釋 编辑

  1. ^ Isobe M, Huebner K, Erikson J, Peterson RC, Bollum FJ, Chang LM, Croce CM. Chromosome localization of the gene for human terminal deoxynucleotidyltransferase to region 10q23-q25. Proc. Natl. Acad. Sci. U.S.A. September 1985, 82 (17): 5836–40. PMC 390648 . PMID 3862101. doi:10.1073/pnas.82.17.5836. 
  2. ^ Yang-Feng TL, Landau NR, Baltimore D, Francke U. The terminal deoxynucleotidyltransferase gene is located on human chromosome 10 (10q23-q24) and on mouse chromosome 19. Cytogenet. Cell Genet. 1986, 43 (3-4): 121–6. PMID 3467897. doi:10.1159/000132309. 
  3. ^ Hardy, Richard. Chapter 7: B Lymphocyte Development and Biology. Paul, William (编). Fundamental Immunology (Book) 6th. Philadelphia: Lippincott Williams & Wilkins. 2008: 237–269. ISBN 0-7817-6519-6. 
  4. ^ Faber J, Kantarjian H, Roberts MW, Keating M, Freireich E, Albitar M. Terminal deoxynucleotidyl transferase-negative acute lymphoblastic leukemia. Arch. Pathol. Lab. Med. January 2000, 124 (1): 92–7. PMID 10629138. 
  5. ^ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M. Manual of Diagnostic Cytology 2. Greenwich Medical Media, Ltd. 2003: 413–414. ISBN 1-84110-100-1. 

延伸阅读 编辑

  • O'Malley DP, Orazi A. Terminal deoxynucleotidyl transferase-positive cells in spleen, appendix and branchial cleft cysts in pediatric patients.. Haematologica. 2006, 91 (8): 1139–40. PMID 16885057. 
  • Yamashita N, Shimazaki N, Ibe S; et al. Terminal deoxynucleotidyltransferase directly interacts with a novel nuclear protein that is homologous to p65.. Genes Cells. 2001, 6 (7): 641–52. PMID 11473582. doi:10.1046/j.1365-2443.2001.00449.x. 
  • Chang LM, Bollum FJ. Molecular biology of terminal transferase.. CRC Crit. Rev. Biochem. 1986, 21 (1): 27–52. PMID 3524991. doi:10.3109/10409238609113608. 
  • Maezawa S, Hayano T, Koiwai K; et al. Bood POZ containing gene type 2 is a human counterpart of yeast Btb3p and promotes the degradation of terminal deoxynucleotidyltransferase.. Genes Cells. 2008, 13 (5): 439–57. PMID 18429817. doi:10.1111/j.1365-2443.2008.01179.x. 
  • Taplin ME, Frantz ME, Canning C; et al. Evidence against T-cell development in the adult human intestinal mucosa based upon lack of terminal deoxynucleotidyltransferase expression.. Immunology. 1996, 87 (3): 402–7. PMC 1384108 . PMID 8778025. doi:10.1046/j.1365-2567.1996.496571.x. 
  • Grupe A, Li Y, Rowland C; et al. A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.. Am. J. Hum. Genet. 2006, 78 (1): 78–88. PMC 1380225 . PMID 16385451. doi:10.1086/498851. 
  • Dworzak MN, Fritsch G, Fröschl G; et al. Four-color flow cytometric investigation of terminal deoxynucleotidyl transferase-positive lymphoid precursors in pediatric bone marrow: CD79a expression precedes CD19 in early B-cell ontogeny.. Blood. 1998, 92 (9): 3203–9. PMID 9787156. 
  • Fujita K, Shimazaki N, Ohta Y; et al. Terminal deoxynucleotidyltransferase forms a ternary complex with a novel chromatin remodeling protein with 82 kDa and core histone.. Genes Cells. 2003, 8 (6): 559–71. PMID 12786946. doi:10.1046/j.1365-2443.2003.00656.x. 
  • Kubota T, Maezawa S, Koiwai K; et al. Identification of functional domains in TdIF1 and its inhibitory mechanism for TdT activity.. Genes Cells. 2007, 12 (8): 941–59. PMID 17663723. doi:10.1111/j.1365-2443.2007.01105.x. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K; et al. Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.. Gene. 1997, 200 (1-2): 149–56. PMID 9373149. doi:10.1016/S0378-1119(97)00411-3. 
  • Bridges SL. Frequent N addition and clonal relatedness among immunoglobulin lambda light chains expressed in rheumatoid arthritis synovia and PBL, and the influence of V lambda gene segment utilization on CDR3 length.. Mol. Med. 1998, 4 (8): 525–53. PMC 2230400 . PMID 9742508. 
  • Liu L, McGavran L, Lovell MA; et al. Nonpositive terminal deoxynucleotidyl transferase in pediatric precursor B-lymphoblastic leukemia.. Am. J. Clin. Pathol. 2004, 121 (6): 810–5. PMID 15198352. doi:10.1309/QD18-PPV1-NH3T-EUTF. 
  • Yang B, Gathy KN, Coleman MS. Mutational analysis of residues in the nucleotide binding domain of human terminal deoxynucleotidyl transferase.. J. Biol. Chem. 1994, 269 (16): 11859–68. PMID 8163485. 
  • Gerhard DS, Wagner L, Feingold EA; et al. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).. Genome Res. 2004, 14 (10B): 2121–7. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504. 
  • Thai TH, Kearney JF. Distinct and opposite activities of human terminal deoxynucleotidyltransferase splice variants.. J. Immunol. 2004, 173 (6): 4009–19. PMID 15356150. 
  • Shimazaki N, Fujita K, Koiwai O. [Expression and function of terminal deoxynucleotidyl-transferase and discovery of novel DNA polymerase mu]. Seikagaku. 2002, 74 (3): 227–32. PMID 11974916. 
  • Mahajan KN, Mitchell BS. Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase.. Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (19): 10746–51. PMC 196874 . PMID 12960389. doi:10.1073/pnas.1631060100. 
  • Strausberg RL, Feingold EA, Grouse LH; et al. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.. Proc. Natl. Acad. Sci. U.S.A. 2002, 99 (26): 16899–903. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899. 
  • Mahajan KN, Gangi-Peterson L, Sorscher DH; et al. Association of terminal deoxynucleotidyl transferase with Ku.. Proc. Natl. Acad. Sci. U.S.A. 1999, 96 (24): 13926–31. PMC 24167 . PMID 10570175. doi:10.1073/pnas.96.24.13926. 
  • Ibe S, Fujita K, Toyomoto T; et al. Terminal deoxynucleotidyltransferase is negatively regulated by direct interaction with proliferating cell nuclear antigen.. Genes Cells. 2001, 6 (9): 815–24. PMID 11554927. doi:10.1046/j.1365-2443.2001.00460.x. 

外部連結 编辑

末端脫氧核苷酸轉移酶, terminal, deoxynucleotidyl, transferase, 末端轉移酶, 是一種特殊的dna, 聚合酶, 顯示出未成熟的, 前b, 前t淋巴細胞, 急性淋巴性白血病, 淋巴瘤細胞, 末端轉移酶, 抗體基因重組時, 加上n核苷酸, nucleotide, 至v, j的外显子上, 能夠形成連接多樣性, junctional, diversity, 的現象, 在人類中, 末端轉移酶是由dntt基因來編碼, tdt不存在於, 胎肝造血干细胞, 而在胎兒期明顯的損害b細胞之連接多. 末端脫氧核苷酸轉移酶 Terminal deoxynucleotidyl transferase TdT 末端轉移酶 是一種特殊的DNA 聚合酶 顯示出未成熟的 前B 前T淋巴細胞 和 急性淋巴性白血病 淋巴瘤細胞 末端轉移酶 於 抗體基因重組時 加上N核苷酸 N nucleotide 至V D J的外显子上 能夠形成連接多樣性 Junctional diversity 的現象 在人類中 末端轉移酶是由DNTT基因來編碼 1 2 TdT不存在於 胎肝造血干细胞 上 而在胎兒期明顯的損害B細胞之連接多樣性 3 目录 1 功能 2 使用 3 參見 4 註釋 5 延伸阅读 6 外部連結功能 编辑 末端轉移酶 催化添加核苷酸至DNA分子的3 末端的反应 不像大多數的DNA聚合酶 它不需要一個模板 這種酶的優選底物是3 突出端 但它也可以添加 核苷酸 nucleotides 至 鈍末端 blunt end 或 凹陷的3 末端 recessed 3 end 钴是一種必要的辅因子 但是在 體外 反应条件下 in vitro 鎂 Mg 及錳 Mn 也可以起相同的作用 使用 编辑末端轉移酶在分子生物學中的應用 它可以被用來在快速擴增cDNA末端 RACE 中來添加 核苷酸 nucleotide 然後可以用來作為在後續PCR的 引物 primer 的模板 它也可以用於添加標記放射性同位素的核苷酸 例如在TUNEL检测 末端脫氧核苷酸轉移酶 dUTP缺口末端標記 dUTP Nick End Labeling 用於细胞凋亡的示範 其中的標記 在某種程度上 通過片段化DNA來進行 也可用於治療 急性淋巴性白血病 診斷之 免疫熒光測定 immuno fluorescence 4 在免疫組織化學中 抗體TdT酶可用於顯示未成熟的T細胞和B細胞以及多能的 造血 Haematopoiesis 幹細胞 的存在 其具有抗原 而成熟的淋巴樣細胞總是呈 TdT陰性 而末端轉移酶陽性的細胞中發現少量的健康淋巴結和扁桃體 急性淋巴細胞白血病的惡性細胞也呈 TdT陽性 而抗體 因此可以被用來作為面板診斷及區別這種疾病的一部分 比如 初發期的小細胞腫瘤 small cell tumours of childhood 5 參見 编辑DNA DNA聚合酶 先天性無子宮無陰道症候群 Mullerian agenesis MRKH 註釋 编辑 Isobe M Huebner K Erikson J Peterson RC Bollum FJ Chang LM Croce CM Chromosome localization of the gene for human terminal deoxynucleotidyltransferase to region 10q23 q25 Proc Natl Acad Sci U S A September 1985 82 17 5836 40 PMC 390648 nbsp PMID 3862101 doi 10 1073 pnas 82 17 5836 Yang Feng TL Landau NR Baltimore D Francke U The terminal deoxynucleotidyltransferase gene is located on human chromosome 10 10q23 q24 and on mouse chromosome 19 Cytogenet Cell Genet 1986 43 3 4 121 6 PMID 3467897 doi 10 1159 000132309 Hardy Richard Chapter 7 B Lymphocyte Development and Biology Paul William 编 Fundamental Immunology Book 6th Philadelphia Lippincott Williams amp Wilkins 2008 237 269 ISBN 0 7817 6519 6 Faber J Kantarjian H Roberts MW Keating M Freireich E Albitar M Terminal deoxynucleotidyl transferase negative acute lymphoblastic leukemia Arch Pathol Lab Med January 2000 124 1 92 7 PMID 10629138 Leong Anthony S Y Cooper Kumarason Leong F Joel W M Manual of Diagnostic Cytology 2 Greenwich Medical Media Ltd 2003 413 414 ISBN 1 84110 100 1 延伸阅读 编辑O Malley DP Orazi A Terminal deoxynucleotidyl transferase positive cells in spleen appendix and branchial cleft cysts in pediatric patients Haematologica 2006 91 8 1139 40 PMID 16885057 Yamashita N Shimazaki N Ibe S et al Terminal deoxynucleotidyltransferase directly interacts with a novel nuclear protein that is homologous to p65 Genes Cells 2001 6 7 641 52 PMID 11473582 doi 10 1046 j 1365 2443 2001 00449 x 引文格式1维护 显式使用等标签 link Chang LM Bollum FJ Molecular biology of terminal transferase CRC Crit Rev Biochem 1986 21 1 27 52 PMID 3524991 doi 10 3109 10409238609113608 Maezawa S Hayano T Koiwai K et al Bood POZ containing gene type 2 is a human counterpart of yeast Btb3p and promotes the degradation of terminal deoxynucleotidyltransferase Genes Cells 2008 13 5 439 57 PMID 18429817 doi 10 1111 j 1365 2443 2008 01179 x 引文格式1维护 显式使用等标签 link Taplin ME Frantz ME Canning C et al Evidence against T cell development in the adult human intestinal mucosa based upon lack of terminal deoxynucleotidyltransferase expression Immunology 1996 87 3 402 7 PMC 1384108 nbsp PMID 8778025 doi 10 1046 j 1365 2567 1996 496571 x 引文格式1维护 显式使用等标签 link Grupe A Li Y Rowland C et al A scan of chromosome 10 identifies a novel locus showing strong association with late onset Alzheimer disease Am J Hum Genet 2006 78 1 78 88 PMC 1380225 nbsp PMID 16385451 doi 10 1086 498851 引文格式1维护 显式使用等标签 link Dworzak MN Fritsch G Froschl G et al Four color flow cytometric investigation of terminal deoxynucleotidyl transferase positive lymphoid precursors in pediatric bone marrow CD79a expression precedes CD19 in early B cell ontogeny Blood 1998 92 9 3203 9 PMID 9787156 引文格式1维护 显式使用等标签 link Fujita K Shimazaki N Ohta Y et al Terminal deoxynucleotidyltransferase forms a ternary complex with a novel chromatin remodeling protein with 82 kDa and core histone Genes Cells 2003 8 6 559 71 PMID 12786946 doi 10 1046 j 1365 2443 2003 00656 x 引文格式1维护 显式使用等标签 link Kubota T Maezawa S Koiwai K et al Identification of functional domains in TdIF1 and its inhibitory mechanism for TdT activity Genes Cells 2007 12 8 941 59 PMID 17663723 doi 10 1111 j 1365 2443 2007 01105 x 引文格式1维护 显式使用等标签 link Suzuki Y Yoshitomo Nakagawa K Maruyama K et al Construction and characterization of a full length enriched and a 5 end enriched cDNA library Gene 1997 200 1 2 149 56 PMID 9373149 doi 10 1016 S0378 1119 97 00411 3 引文格式1维护 显式使用等标签 link Bridges SL Frequent N addition and clonal relatedness among immunoglobulin lambda light chains expressed in rheumatoid arthritis synovia and PBL and the influence of V lambda gene segment utilization on CDR3 length Mol Med 1998 4 8 525 53 PMC 2230400 nbsp PMID 9742508 Liu L McGavran L Lovell MA et al Nonpositive terminal deoxynucleotidyl transferase in pediatric precursor B lymphoblastic leukemia Am J Clin Pathol 2004 121 6 810 5 PMID 15198352 doi 10 1309 QD18 PPV1 NH3T EUTF 引文格式1维护 显式使用等标签 link Yang B Gathy KN Coleman MS Mutational analysis of residues in the nucleotide binding domain of human terminal deoxynucleotidyl transferase J Biol Chem 1994 269 16 11859 68 PMID 8163485 Gerhard DS Wagner L Feingold EA et al The status quality and expansion of the NIH full length cDNA project the Mammalian Gene Collection MGC Genome Res 2004 14 10B 2121 7 PMC 528928 nbsp PMID 15489334 doi 10 1101 gr 2596504 引文格式1维护 显式使用等标签 link Thai TH Kearney JF Distinct and opposite activities of human terminal deoxynucleotidyltransferase splice variants J Immunol 2004 173 6 4009 19 PMID 15356150 Shimazaki N Fujita K Koiwai O Expression and function of terminal deoxynucleotidyl transferase and discovery of novel DNA polymerase mu Seikagaku 2002 74 3 227 32 PMID 11974916 Mahajan KN Mitchell BS Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase Proc Natl Acad Sci U S A 2003 100 19 10746 51 PMC 196874 nbsp PMID 12960389 doi 10 1073 pnas 1631060100 Strausberg RL Feingold EA Grouse LH et al Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proc Natl Acad Sci U S A 2002 99 26 16899 903 PMC 139241 nbsp PMID 12477932 doi 10 1073 pnas 242603899 引文格式1维护 显式使用等标签 link Mahajan KN Gangi Peterson L Sorscher DH et al Association of terminal deoxynucleotidyl transferase with Ku Proc Natl Acad Sci U S A 1999 96 24 13926 31 PMC 24167 nbsp PMID 10570175 doi 10 1073 pnas 96 24 13926 引文格式1维护 显式使用等标签 link Ibe S Fujita K Toyomoto T et al Terminal deoxynucleotidyltransferase is negatively regulated by direct interaction with proliferating cell nuclear antigen Genes Cells 2001 6 9 815 24 PMID 11554927 doi 10 1046 j 1365 2443 2001 00460 x 引文格式1维护 显式使用等标签 link 外部連結 编辑醫學主題詞表 MeSH Terminal 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