末端去氧核苷酸轉移酶

末端去氧核苷酸轉移酶（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的外顯子上，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"胎肝造血幹細胞"上，而在胎兒期明顯的損害B細胞之連接多樣性。^[3]

功能

"末端轉移酶"催化添加核苷酸至DNA分子的3'末端的反應。不像大多數的DNA聚合酶，它不需要一個模板。這種酶的優選受質是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)。鈷是一種必要的輔因子，但是在"體外"反應條件下(in vitro)鎂(Mg)及錳(Mn)也可以起相同的作用。

使用

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"引子"(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檢測(末端去氧核苷酸轉移酶"dUTP缺口末端標記"(dUTP Nick End Labeling))，用於細胞凋亡的示範(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"免疫螢光測定"(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，急性淋巴球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

註釋

^ 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.
^ 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 (編). Fundamental Immunology (Book) 6th. Philadelphia: Lippincott Williams & 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.

延伸閱讀

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

醫學主題詞表（MeSH）：Terminal+Deoxyribonucleotidyltransferase

[pmid3862101-1] 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.

[pmid3467897-2] 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.

[Paul0807-3] Hardy, Richard. Chapter 7: B Lymphocyte Development and Biology. Paul, William (編). Fundamental Immunology (Book) 6th. Philadelphia: Lippincott Williams & Wilkins. 2008: 237–269. ISBN 0-7817-6519-6.

[pmid10629138-4] 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.

[Leong-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.

[1]

[2]

[3]

[4]

[5]