末端脱氧核苷酸转移酶

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末端脱氧核苷酸转移酶(Terminal deoxynucleotidyl transferasTdT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]

目录

功能

"末端转移酶"催化的加上核苷酸至DNA分子3'末端。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3'突出端,但它也可以添加"核苷酸"(nucleotifes)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,但是在酶催化后反应在的镁(Mg)及锰(Mn)施用"体外"(in vitro)。

使用

末端转移酶在分子生物学中的应用。它可以被用来在cDNA末端的快速扩增(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]

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

  1. 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. 
  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. doi:10.1159/000132309. PMID 3467897. 
  3. 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. 
  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: 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, 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. 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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