末端脱氧核苷酸转移酶

末端脱氧核苷酸转移酶（Terminal deoxynucleotidyl transferase、TdT、末端转移酶），是一种特殊的DNA聚合酶，显示出未成熟的、"前B"，"前T淋巴细胞"和"急性淋巴性白血病/淋巴瘤细胞"。"末端转移酶"于"抗体基因重组时"加上N核苷酸（N-nucleotide）至V(D)J的外显子上，能够形成连接多样性（Junctional diversity）的现象。在人类中，末端转移酶是由DNTT基因来编码。 ^[1]^[2]

TdT不存在于"胎肝造血干细胞"上，而在胎儿期明显的损害B细胞之连接多样性。^[3]

功能

"末端转移酶"催化添加核苷酸至DNA分子的3'末端的反应。不像大多数的DNA聚合酶，它不需要一个模板。这种酶的优选底物是3'突出端，但它也可以添加"核苷酸"(nucleotides)至"钝末端"(blunt end)或"凹陷的3'末端"(recessed 3' end)。钴是一种必要的辅因子，但是在"体外"反应条件下(in vitro)镁(Mg)及锰(Mn)也可以起相同的作用。

使用

末端转移酶在分子生物学中的应用。它可以被用来在快速扩增cDNA末端(RACE)中来添加"核苷酸"(nucleotide)，然后可以用来作为在后续PCR的"引物"(primer)的模板。它也可以用于添加标记放射性同位素的核苷酸，例如在TUNEL检测(末端脱氧核苷酸转移酶"dUTP缺口末端标记"(dUTP Nick End Labeling))，用于细胞凋亡的示范(其中的标记，在某种程度上，通过片段化DNA来进行)。也可用于治疗"急性淋巴性白血病"诊断之"免疫荧光测定"(immuno-fluorescence)。^[4]

在免疫组织化学中，抗体TdT酶可用于显示未成熟的T细胞和B细胞以及多能的"造血(Haematopoiesis)干细胞"的存在，其具有抗原，而成熟的淋巴样细胞总是呈"TdT阴性"。而末端转移酶阳性的细胞中发现少量的健康淋巴结和扁桃体，急性淋巴细胞白血病的恶性细胞也呈"TdT阳性"，而抗体，因此可以被用来作为面板诊断及区别这种疾病的一部分，比如，"初发期的小细胞肿瘤"(small cell tumours of childhood)。^[5]

参见

注释

^ 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 (编). 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.

延伸阅读

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.
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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.
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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.

外部链接

医学主题词表（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 (编). 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.

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