Antibody class switching mediated by yeast endonuclease-generated DNA breaks.

作者: A. A. Zarrin , C. Del Vecchio , E. Tseng , M. Gleason , P. Zarin

DOI: 10.1126/SCIENCE.1136386

关键词: Cytidine deaminaseImmunoglobulin heavy chainDNA repairMolecular biologyEndonucleaseActivation-induced (cytidine) deaminaseLocus (genetics)MutantImmunoglobulin class switchingBiology

摘要: Antibody class switching in activated B cells uses switch recombination (CSR), which joins activation-induced cytidine deaminase (AID)–dependent double-strand breaks (DSBs) within two large immunoglobulin heavy chain (IgH) locus (S) regions that lie up to 200 kilobases apart. To test postulated roles of S and AID CSR, we generated mutant donor Sμ accepter Sγ1 were replaced with yeast I-SceI endonuclease sites. We found site-specific DSBs mediate recombinational IgH from IgM IgG1 without or AID. propose CSR evolved exploit a general DNA repair process promotes joining widely separated chromosome.

参考文章(30)
Christine Richardson, Maria Jasin, Frequent chromosomal translocations induced by DNA double-strand breaks Nature. ,vol. 405, pp. 697- 700 ,(2000) , 10.1038/35015097
Darryll D. Dudley, Jayanta Chaudhuri, Craig H. Bassing, Frederick W. Alt, Mechanism and Control of V(D)J Recombination versus Class Switch Recombination: Similarities and Differences Advances in Immunology. ,vol. 86, pp. 43- 112 ,(2005) , 10.1016/S0065-2776(04)86002-4
Amy L. Kenter, Robert A. Wuerffel, Rebecca J. Thompson, Jian Du, Ig Sgamma3 DNA-specifc double strand breaks are induced in mitogen-activated B cells and are implicated in switch recombination. Journal of Immunology. ,vol. 159, pp. 4139- 4144 ,(1997)
G.D. Yancopoulos, R.A. DePinho, K.A. Zimmerman, S.G. Lutzker, N. Rosenberg, F.W. Alt, Secondary genomic rearrangement events in pre-B cells: VHDJH replacement by a LINE-1 sequence and directed class switching. The EMBO Journal. ,vol. 5, pp. 3259- 3266 ,(1986) , 10.1002/J.1460-2075.1986.TB04637.X
Ahmed Amine Khamlichi, Florence Glaudet, Zeliha Oruc, Vincent Denis, Marc Le Bert, Michel Cogné, Immunoglobulin class-switch recombination in mice devoid of any Sμ tandem repeat Blood. ,vol. 103, pp. 3828- 3836 ,(2004) , 10.1182/BLOOD-2003-10-3470
Ali A Zarrin, Frederick W Alt, Jayanta Chaudhuri, Nicole Stokes, Dhruv Kaushal, Louis Du Pasquier, Ming Tian, An evolutionarily conserved target motif for immunoglobulin class-switch recombination. Nature Immunology. ,vol. 5, pp. 1275- 1281 ,(2004) , 10.1038/NI1137
J. Chen, R. Lansford, V. Stewart, F. Young, F. W. Alt, RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 90, pp. 4528- 4532 ,(1993) , 10.1073/PNAS.90.10.4528
Reiko Shinkura, Ming Tian, Michele Smith, Katrin Chua, Yuko Fujiwara, Frederick W. Alt, The influence of transcriptional orientation on endogenous switch region function. Nature Immunology. ,vol. 4, pp. 435- 441 ,(2003) , 10.1038/NI918