The recruitment of activation induced cytidine deaminase to the immunoglobulin locus by a regulatory element

被引:5
作者
Kim, Yonghwan [1 ]
Tian, Ming [1 ]
机构
[1] Univ Texas Austin, Sect Mol Genet & Microbiol, Austin, TX 78712 USA
关键词
Immunoglobulin; Gene conversion; Transcription; AID; Enhancers; CLASS-SWITCH RECOMBINATION; PROTEIN-KINASE-A; SOMATIC HYPERMUTATION; GENE CONVERSION; DIVERSIFICATION ENZYME; AID; DNA; TARGETS; TRANSCRIPTION; EXPRESSION;
D O I
10.1016/j.molimm.2010.02.025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation induced cytidine deaminase (AID) is critical for the diversification of immunoglobulin (Ig). AID is generally thought to function by deaminating cytidines into uridines in the target DNA within the Ig loci, and the subsequent processing of the uridines, through DNA repair or replication, could lead to three different forms of Ig diversification events: class switch recombination, somatic hypermutation and gene conversion. Although AID is important for effective immunity, its mutagenic activity needs to be restricted to the Ig loci in order to avoid rampant mutations in the genome. In our previous studies, we have identified an Ig lambda regulatory element (Region A) that is important for AID mediated gene conversion in chicken B cells, but its mechanism of function was unclear. In this report, we provide evidence that the regulatory element plays a role in recruiting AID to the Ig lambda locus. (c) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1860 / 1865
页数:6
相关论文
共 30 条
[1]   Mutants IoxP vectors for selectable marker recycle and conditional knock-outs [J].
Arakawa H. ;
Lodygin D. ;
Buerstedde J.-M. .
BMC Biotechnology, 1 (1)
[2]   Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion [J].
Arakawa, H ;
Hauschild, J ;
Buerstedde, JM .
SCIENCE, 2002, 295 (5558) :1301-1306
[3]   The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation [J].
Basu, U ;
Chaudhuri, J ;
Alpert, C ;
Dutt, S ;
Ranganath, S ;
Li, G ;
Schrum, JP ;
Manis, JP ;
Alt, FW .
NATURE, 2005, 438 (7067) :508-511
[4]   A cis-Acting Diversification Activator Both Necessary and Sufficient for AID-Mediated Hypermutation [J].
Blagodatski, Artem ;
Batrak, Vera ;
Schmidl, Sabine ;
Schoetz, Ulrike ;
Caldwell, Randolph B. ;
Arakawa, Hiroshi ;
Buerstedde, Jean-Marie .
PLOS GENETICS, 2009, 5 (01)
[5]   Replication protein A interacts with AID to promote deamination of somatic hypermutation targets [J].
Chaudhuri, J ;
Khuong, C ;
Alt, FW .
NATURE, 2004, 430 (7003) :992-998
[6]   Interaction between anti body-diversification enzyme AID and spliceosome-associated factor CTNNBL1 [J].
Conticello, Silvestro G. ;
Ganesh, Karuna ;
Xue, Kanmin ;
Lu, Mason ;
Rada, Cristina ;
Neuberger, Michael S. .
MOLECULAR CELL, 2008, 31 (04) :474-484
[7]   Molecular mechanisms of antibody somatic hypermutation [J].
Di Nola, Javier M. ;
Neuberger, Michael S. .
ANNUAL REVIEW OF BIOCHEMISTRY, 2007, 76 :1-22
[8]   Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA [J].
Duquette, ML ;
Handa, P ;
Vincent, JA ;
Taylor, AF ;
Maizels, N .
GENES & DEVELOPMENT, 2004, 18 (13) :1618-1629
[9]   Non-redundancy of cytidine deaminases in class switch recombination [J].
Fugmann, SD ;
Rush, JS ;
Schatz, DG .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (03) :844-849
[10]   AID is essential for immunoglobulin V gene conversion in a cultured B cell line [J].
Harris, RS ;
Sale, JE ;
Petersen-Mahrt, SK ;
Neuberger, MS .
CURRENT BIOLOGY, 2002, 12 (05) :435-438