激活诱导性胞苷脱氨酶
激活诱导性胞苷脱氨酶（Activation-induced cytidine deaminase，简称AID）是一种胞苷脱氨酶，属APOBEC脱氨酶家族，在人类基因组中由12号染色体上的AICDA基因编码，大小约为24kDa[6]，可催化胞苷（C）脱氨转为尿苷（U）的反应，即将DNA上的C:G配对转为U:G误配，且因DNA复制时会将U视为T，最终会导致U:G转为T:A的转换突变[7][8]。U:G误配也可能被细胞中的碱基切除修复（BER）或错误配对修复（MMR）机制修补，BER途径中此误配可被尿嘧啶DNA糖基酶（UDG）识别而切除，形成AP位点，接着可能由DNA聚合酶η等易误（error-prone）的聚合酶随机补上碱基而完成修补（短补丁修复），或将下游数个碱基由内切酶切除后再合成新的核苷酸以完成修补（长补丁修复）[9]；MMR途径中，U:G误配则会被MutSα复合体识别而被切除，再由易误的聚合酶随机补上碱基，两种修复机制皆可能造成突变[10]。DNA转录时暂时呈单股的状态有利于激活诱导性胞苷脱氨酶的催化反应[11][12]。
激活诱导性胞苷脱氨酶最早于1999年由日本免疫学家本庶佑发现[13]，此酵素在免疫系统中有重要功能，B细胞在淋巴结的生发中心进行亲和力成熟的过程中，催化C脱氨转为U的反应以造成DNA断裂，促进体细胞高频突变、免疫球蛋白类型转换和基因转换等增加抗体多样性的重要机制[14]。较新的研究显示除B细胞外还有其他组织有表现激活诱导性胞苷脱氨酶，且除催化C-U转换之外，激活诱导性胞苷脱氨酶还可催化5-甲基胞嘧啶脱氨转为胸腺嘧啶（T），因而有去甲基酶的功能，可能参与基因的表观遗传学调控[15][16]。
B细胞中有数种调控激活诱导性胞苷脱氨酶活性的机制，例如此蛋白上有许多可能调控其活性的磷酸化位点[14]。此蛋白的表现异常与数种疾病有关，此基因的缺乏会导致第二型高免疫球蛋白M综合征[17]，其过度表现则可能与数种B细胞淋巴瘤有关[14][18]。
参考文献
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- ^ 與活化誘導胞苷脫氨酶相關的疾病；在維基數據上查看/編輯參考.
- ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000111732 - Ensembl, May 2017
- ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000040627 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Entrez Gene: AICDA activation-induced cytidine deaminase.
- ^ Petersen-Mahrt, Svend K.; Harris, Reuben S.; Neuberger, Michael S. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature. 2002-07-04, 418 (6893): 99–103 [2021-04-29]. ISSN 0028-0836. PMID 12097915. doi:10.1038/nature00862. （原始内容存档于2021-02-05）.
- ^ Q9GZX7 (AICDA_HUMAN). [26 January 2013]. （原始内容存档于2021-06-04）.
- ^ Pilzecker B, Jacobs H. Mutating for Good: DNA Damage Responses During Somatic Hypermutation.. Front Immunol. 2019, 10: 438. PMC 6423074
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- ^ Senavirathne G, Bertram JG, Jaszczur M, Chaurasiya KR, Pham P, Mak CH; et al. Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution.. Nat Commun. 2015, 6: 10209. PMC 4703863 . PMID 26681117. doi:10.1038/ncomms10209.
- ^ Ramiro AR, Stavropoulos P, Jankovic M, Nussenzweig MC. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand.. Nat Immunol. 2003, 4 (5): 452–6. PMID 12692548. doi:10.1038/ni920.
- ^ Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, Davidson NO; et al. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells.. J Biol Chem. 1999, 274 (26): 18470–6. PMID 10373455. doi:10.1074/jbc.274.26.18470.
- ^ 14.0 14.1 14.2 Robbiani DF, Nussenzweig MC. Chromosome translocation, B cell lymphoma, and activation-induced cytidine deaminase.. Annu Rev Pathol. 2013, 8: 79–103. PMID 22974238. doi:10.1146/annurev-pathol-020712-164004.
- ^ Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming.. J Biol Chem. 2004, 279 (50): 52353–60. PMID 15448152. doi:10.1074/jbc.M407695200.
- ^ Dominguez PM, Shaknovich R. Epigenetic function of activation-induced cytidine deaminase and its link to lymphomagenesis.. Front Immunol. 2014, 5: 642. PMC 4270259 . PMID 25566255. doi:10.3389/fimmu.2014.00642.
- ^ Luo Z, Ronai D, Scharff MD. The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies. J. Allergy Clin. Immunol. 2004, 114 (4): 726–35; quiz 736. PMID 15480307. doi:10.1016/j.jaci.2004.07.049.
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