末端脫氧核苷酸轉移酶
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末端脫氧核苷酸轉移酶(Terminal deoxynucleotidyl transferas、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"于"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不存在于"胎肝造血干細胞"上，而在胎兒期明顯的損害B細胞之連接多樣性。[3]
目錄 |
功能
"末端轉移酶"催化的加上核苷酸至DNA分子的3'末端。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"(nucleotifes)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，但是在酶催化后反應在的鎂(Mg)及錳(Mn)施用"體外"(in vitro)。
使用
末端轉移酶在分子生物學中的應用。它可以被用來在cDNA末端的快速擴增(RACE)中來添加"核苷酸"(nucleotide)，然后可以用來作為在后續PCR的"引物"(primer)的模板。它也可以用于添加標記放射性同位素的核苷酸，例如在TUNEL檢測(末端脫氧核苷酸轉移酶"dUTP缺口末端標記"(dUTP Nick End Labeling))，用于細胞凋亡的示范(其中的標記，在某種程度上，通過片段化DNA來進行)。也可用于治療"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酶可用于顯示未成熟的T細胞和B細胞以及多能的"造血(Haematopoiesis)干細胞"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
- DNA
- DNA聚合酶
- 先天性無子宮無陰道癥候群(Müllerian agenesis/MRKH)
注釋
- ↑ Isobe M, Huebner K, Erikson J, Peterson RC, Bollum FJ, Chang LM, Croce CM. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC390648/ 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. doi:10.1073/pnas.82.17.5836. PMID 3862101. PMC 390648.
- ↑ 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. doi:10.1159/000132309. PMID 3467897.
- ↑ Hardy, Richard. Chapter 7: B Lymphocyte Development and Biology//Paul, William. Fundamental Immunology (Book). 6th. Philadelphia: Lippincott Williams & Wilkins. 2008: pp. 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: pp. 413–414. ISBN 1-84110-100-1.
Further reading
- 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. doi:10.1046/j.1365-2443.2001.00449.x. PMID 11473582.
- Chang LM, Bollum FJ. Molecular biology of terminal transferase.. CRC Crit. Rev. Biochem.. 1986, 21 (1): 27–52. doi:10.3109/10409238609113608. PMID 3524991.
- 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. doi:10.1111/j.1365-2443.2008.01179.x. PMID 18429817.
- Taplin ME, Frantz ME, Canning C, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1384108/ Evidence against T-cell development in the adult human intestinal mucosa based upon lack of terminal deoxynucleotidyltransferase expression.]. Immunology. 1996, 87 (3): 402–7. doi:10.1046/j.1365-2567.1996.496571.x. PMID 8778025. PMC 1384108.
- Grupe A, Li Y, Rowland C, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC1380225/ 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. doi:10.1086/498851. PMID 16385451. PMC 1380225.
- Dworzak MN, Fritsch G, Fr?schl 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. doi:10.1046/j.1365-2443.2003.00656.x. PMID 12786946.
- 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. doi:10.1111/j.1365-2443.2007.01105.x. PMID 17663723.
- 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. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Bridges SL. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2230400/ 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. PMID 9742508. PMC 2230400.
- 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. doi:10.1309/QD18-PPV1-NH3T-EUTF. PMID 15198352.
- 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.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC528928/ The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).]. Genome Res.. 2004, 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334. PMC 528928.
- 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. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC196874/ 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. doi:10.1073/pnas.1631060100. PMID 12960389. PMC 196874.
- Strausberg RL, Feingold EA, Grouse LH, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC139241/ 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. doi:10.1073/pnas.242603899. PMID 12477932. PMC 139241.
- Mahajan KN, Gangi-Peterson L, Sorscher DH, et al.. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC24167/ Association of terminal deoxynucleotidyl transferase with Ku.]. Proc. Natl. Acad. Sci. U.S.A.. 1999, 96 (24): 13926–31. doi:10.1073/pnas.96.24.13926. PMID 10570175. PMC 24167.
- 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. doi:10.1046/j.1365-2443.2001.00460.x. PMID 11554927.
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