转录延伸复合物指导激活诱导的胞嘧啶脱氨酶介导的DNA脱氨基作用。
The transcription elongation complex directs activation-induced cytidine deaminase-mediated DNA deamination.
作者信息
Besmer Eva, Market Eleonora, Papavasiliou F Nina
机构信息
Laboratory of Lymphocyte Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
出版信息
Mol Cell Biol. 2006 Jun;26(11):4378-85. doi: 10.1128/MCB.02375-05.
Abstract
Activation-induced cytidine deaminase (AID) is a single-stranded DNA deaminase required for somatic hypermutation of immunoglobulin (Ig) genes, a key process in the development of adaptive immunity. Transcription provides a single-stranded DNA substrate for AID, both in vivo and in vitro. We present here an assay which can faithfully replicate all of the molecular features of the initiation of hypermutation of Ig genes in vivo. In this assay, which detects AID-mediated deamination in the context of transcription by Escherichia coli RNA polymerase, deamination targets either strand and declines in efficiency as the distance from the promoter increases. We show that AID binds DNA exposed by the transcribing polymerase, implicating the polymerase itself as the vehicle which distributes AID on DNA as it moves away from the promoter.
摘要
激活诱导的胞嘧啶脱氨酶（AID）是一种单链DNA脱氨酶，是免疫球蛋白（Ig）基因体细胞超突变所必需的，而体细胞超突变是适应性免疫发育中的关键过程。无论是在体内还是体外，转录都为AID提供单链DNA底物。我们在此展示一种检测方法，它能够如实地复制体内Ig基因超突变起始的所有分子特征。在该检测方法中，通过大肠杆菌RNA聚合酶在转录背景下检测AID介导的脱氨作用，脱氨作用可靶向任一条链，并且随着与启动子距离的增加，效率会降低。我们发现AID结合由转录聚合酶暴露的DNA，这表明聚合酶本身就是在其远离启动子移动时将AID分布于DNA上的载体。
相似文献
1
The transcription elongation complex directs activation-induced cytidine deaminase-mediated DNA deamination.转录延伸复合物指导激活诱导的胞嘧啶脱氨酶介导的DNA脱氨基作用。
Mol Cell Biol. 2006 Jun;26(11):4378-85. doi: 10.1128/MCB.02375-05.
2
Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand.转录通过在非模板链上暴露单链DNA来增强AID介导的胞嘧啶脱氨作用。
Nat Immunol. 2003 May;4(5):452-6. doi: 10.1038/ni920.
3
Transcription-targeted DNA deamination by the AID antibody diversification enzyme.由AID抗体多样化酶进行的靶向转录的DNA脱氨基作用。
Nature. 2003 Apr 17;422(6933):726-30. doi: 10.1038/nature01574. Epub 2003 Apr 9.
4
Deoxyuridine is generated preferentially in the nontranscribed strand of DNA from cells expressing activation-induced cytidine deaminase.脱氧尿苷优先在表达活化诱导胞苷脱氨酶的细胞的DNA非转录链中产生。
J Immunol. 2005 Jun 15;174(12):7787-91. doi: 10.4049/jimmunol.174.12.7787.
5
Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations.人类激活诱导的胞苷脱氨酶导致转录依赖性、链偏向性的C到U脱氨作用。
Nucleic Acids Res. 2003 Jun 15;31(12):2990-4. doi: 10.1093/nar/gkg464.
6
A combined nuclear and nucleolar localization motif in activation-induced cytidine deaminase (AID) controls immunoglobulin class switching.激活诱导胞苷脱氨酶（AID）中的核和核仁定位基序的组合控制免疫球蛋白类别转换。
J Mol Biol. 2013 Jan 23;425(2):424-43. doi: 10.1016/j.jmb.2012.11.026. Epub 2012 Nov 23.
7
Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation.进行性AID催化的单链DNA胞嘧啶脱氨基模拟体细胞高频突变。
Nature. 2003 Jul 3;424(6944):103-7. doi: 10.1038/nature01760. Epub 2003 Jun 18.
8
Replication protein A interacts with AID to promote deamination of somatic hypermutation targets.复制蛋白A与活化诱导胞嘧啶脱氨酶相互作用，以促进体细胞高频突变靶点的脱氨作用。
Nature. 2004 Aug 26;430(7003):992-8. doi: 10.1038/nature02821. Epub 2004 Jul 25.
9
Activation-induced cytidine deaminase acts on double-strand breaks in vitro.活化诱导的胞苷脱氨酶在体外作用于双链断裂。
Mol Immunol. 2007 Feb;44(5):974-83. doi: 10.1016/j.molimm.2006.03.015. Epub 2006 May 11.
10
AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification.活化诱导胞嘧啶脱氨酶使大肠杆菌发生突变，提示抗体多样化存在DNA脱氨基机制。
Nature. 2002 Jul 4;418(6893):99-103. doi: 10.1038/nature00862.
引用本文的文献
1
Human activation-induced deaminase lacks strong replicative strand bias or preference for cytosines in hairpin loops.人类激活诱导脱氨酶在发夹环中缺乏强烈的复制链偏向或对胞嘧啶的偏好。
Nucleic Acids Res. 2022 May 20;50(9):5145-5157. doi: 10.1093/nar/gkac296.
2
Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes.Dot1L 和 H3K79 甲基化在调节免疫球蛋白基因体细胞超突变中的作用。
Proc Natl Acad Sci U S A. 2021 Jul 20;118(29). doi: 10.1073/pnas.2104013118.
3
Immunoinformatics approach for multi-epitope vaccine design against structural proteins and ORF1a polyprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）结构蛋白和ORF1a多聚蛋白的多表位疫苗设计的免疫信息学方法
Trop Dis Travel Med Vaccines. 2021 Jul 8;7(1):22. doi: 10.1186/s40794-021-00147-1.
4
Simultaneous in vitro characterisation of DNA deaminase function and associated DNA repair pathways.同时进行体外 DNA 脱氨酶功能及其相关 DNA 修复途径的表征。
PLoS One. 2013 Dec 9;8(12):e82097. doi: 10.1371/journal.pone.0082097. eCollection 2013.
5
E3-ubiquitin ligase Nedd4 determines the fate of AID-associated RNA polymerase II in B cells.E3 泛素连接酶 Nedd4 决定了 B 细胞中 AID 相关 RNA 聚合酶 II 的命运。
Genes Dev. 2013 Aug 15;27(16):1821-33. doi: 10.1101/gad.210211.112.
6
Transcriptional stalling in B-lymphocytes: a mechanism for antibody diversification and maintenance of genomic integrity.B淋巴细胞中的转录停滞：抗体多样化和基因组完整性维持的一种机制。
Transcription. 2013 May-Jun;4(3):127-35. doi: 10.4161/trns.24556. Epub 2013 Apr 12.
7
Identification of core DNA elements that target somatic hypermutation.鉴定靶向体细胞高频突变的核心 DNA 元件。
J Immunol. 2012 Dec 1;189(11):5314-26. doi: 10.4049/jimmunol.1202082. Epub 2012 Oct 19.
8
Three-dimensional architecture of the IgH locus facilitates class switch recombination.免疫球蛋白重链（IgH）基因座的三维结构促进类别转换重组。
Ann N Y Acad Sci. 2012 Sep;1267(1):86-94. doi: 10.1111/j.1749-6632.2012.06604.x.
9
AID targeting is dependent on RNA polymerase II pausing.AID 靶向依赖于 RNA 聚合酶 II 的暂停。
Semin Immunol. 2012 Aug;24(4):281-6. doi: 10.1016/j.smim.2012.06.001. Epub 2012 Jul 10.
10
Requirement of upstream Hfq-binding (ARN)x elements in glmS and the Hfq C-terminal region for GlmS upregulation by sRNAs GlmZ and GlmY.上游 Hfq 结合 (ARN)x 元件和 Hfq C 末端区域在 glmS 上调中的要求 GlmZ 和 GlmY 的 sRNAs。
Nucleic Acids Res. 2012 Sep;40(16):8021-32. doi: 10.1093/nar/gks392. Epub 2012 May 31.
本文引用的文献
1
Targeting of the activation-induced cytosine deaminase is strongly influenced by the sequence and structure of the targeted DNA.活化诱导胞嘧啶脱氨酶的靶向作用受到靶向DNA的序列和结构的强烈影响。
Mol Cell Biol. 2005 Dec;25(24):10815-21. doi: 10.1128/MCB.25.24.10815-10821.2005.
2
The very 5' end and the constant region of Ig genes are spared from somatic mutation because AID does not access these regions.免疫球蛋白（Ig）基因的5'端最末端和恒定区不会发生体细胞突变，因为激活诱导胞苷脱氨酶（AID）无法作用于这些区域。
J Exp Med. 2005 Nov 21;202(10):1443-54. doi: 10.1084/jem.20051604.
3
The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation.艾滋病抗体多样化酶受蛋白激酶A磷酸化作用调控。
Nature. 2005 Nov 24;438(7067):508-11. doi: 10.1038/nature04255. Epub 2005 Oct 26.
4
The BRCA2 homologue Brh2 nucleates RAD51 filament formation at a dsDNA-ssDNA junction.BRCA2的同源物Brh2在双链DNA-单链DNA连接处促使RAD51丝状物形成。
Nature. 2005 Feb 10;433(7026):653-7. doi: 10.1038/nature03234.
5
Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases.多核苷酸（脱氧）胞苷脱氨酶的AID/APOBEC家族的进化
Mol Biol Evol. 2005 Feb;22(2):367-77. doi: 10.1093/molbev/msi026. Epub 2004 Oct 20.
6
Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation.错配识别和尿嘧啶切除为免疫球蛋白类别转换和体细胞突变的A/T集中阶段提供了互补途径。
Mol Cell. 2004 Oct 22;16(2):163-71. doi: 10.1016/j.molcel.2004.10.011.
7
Biochemical analysis of hypermutational targeting by wild type and mutant activation-induced cytidine deaminase.野生型和突变型激活诱导胞苷脱氨酶对高突变靶向的生化分析。
J Biol Chem. 2004 Dec 3;279(49):51612-21. doi: 10.1074/jbc.M408135200. Epub 2004 Sep 14.
8
Replication protein A interacts with AID to promote deamination of somatic hypermutation targets.复制蛋白A与活化诱导胞嘧啶脱氨酶相互作用，以促进体细胞高频突变靶点的脱氨作用。
Nature. 2004 Aug 26;430(7003):992-8. doi: 10.1038/nature02821. Epub 2004 Jul 25.
9
Class-switch recombination: interplay of transcription, DNA deamination and DNA repair.类别转换重组：转录、DNA脱氨基与DNA修复的相互作用
Nat Rev Immunol. 2004 Jul;4(7):541-52. doi: 10.1038/nri1395.
10
The structural basis of the transition from initiation to elongation phases of transcription, as well as translocation and strand separation, by T7 RNA polymerase.T7 RNA聚合酶介导的转录从起始阶段到延伸阶段的转变以及转位和链分离的结构基础。
Curr Opin Struct Biol. 2004 Feb;14(1):4-9. doi: 10.1016/j.sbi.2004.01.006.
Zotero 插件