活化诱导性胞苷脱氨酶
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活化诱导性胞苷脱氨酶(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,接著可能由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活化诱导性胞苷脱氨酶的催化反应[11][12]。
活化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,促进体细胞超突变、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活化诱导性胞苷脱氨酶,且除催化C-U转换之外,活化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细胞中有数种调控活化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症候群[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
[编辑]- ^ 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
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- ^ 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.
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