Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions

被引：99

作者：

Maul, Robert W. ^{[1
]}

Saribasak, Huseyin ^{[1
]}

Martomo, Stella A. ^{[1
]}

McClure, Rhonda L. ^{[1
]}

Yang, William ^{[1
]}

Vaisman, Alexandra ^{[2
]}

Gramlich, Hillary S. ^{[3
]}

Schatz, David G. ^{[4
]}

Woodgate, Roger ^{[2
]}

Wilson, David M., III ^{[1
]}

Gearhart, Patricia J. ^{[1
]}

机构：

[1] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA

[2] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA

[3] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Cell Biol, New Haven, CT 06510 USA

[4] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Immunol, New Haven, CT 06510 USA

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 01期

基金：

美国国家卫生研究院;

关键词：

DNA GLYCOSYLASE ACTIVITY; SINGLE-STRANDED-DNA; LIGHT-CHAIN GENE; SOMATIC HYPERMUTATION; R-LOOPS; RECOMBINATION; CONVERSION; CELLS; DIVERSIFICATION; DEOXYCYTIDINE;

D O I：

10.1038/ni.1970

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Activation-induced deaminase (AID) initiates diversity of immunoglobulin genes through deamination of cytosine to uracil. Two opposing models have been proposed for the deamination of DNA or RNA by AID. Although most data support DNA deamination, there is no physical evidence of uracil residues in immunoglobulin genes. Here we demonstrate their presence by determining the sensitivity of DNA to digestion with uracil DNA glycosylase (UNG) and abasic endonuclease. Using several methods of detection, we identified uracil residues in the variable and switch regions. Uracil residues were generated within 24 h of B cell stimulation, were present on both DNA strands and were found to replace mainly cytosine bases. Our data provide direct evidence for the model that AID functions by deaminating cytosine residues in DNA.

引用

页码：70 / U93

页数：8

共 55 条

[1] CLONAL GROWTH AND MATURATION TO IMMUNOGLOBULIN SECRETION INVITRO OF EVERY GROWTH-INDUCIBLE B LYMPHOCYTE [J].

ANDERSSON, J ;

COUTINHO, A ;

LERNHARDT, W ;

MELCHERS, F .

CELL, 1977, 10 (01) :27-34

[2] Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate [J].

Arakawa, H ;

Saribasak, H ;

Buerstedde, JM .

PLOS BIOLOGY, 2004, 2 (07) :967-974

[3] Uracil DNA glycosylase activity is dispensable for immunloglobulin class switch [J].

Begum, NA ;

Kinoshita, K ;

Kakazu, N ;

Muramatsu, M ;

Nagaoka, H ;

Shinkura, R ;

Biniszkiewicz, D ;

Boyer, LA ;

Jaenisch, R ;

Honjo, T .

SCIENCE, 2004, 305 (5687) :1160-1163

[4] Requirement of non-canonical activity of uracil DNA glycosylase for class switch recombination [J].

Begum, Nasim A. ;

Izumi, Nakako ;

Nishikori, Momoko ;

Nagaoka, Hitoshi ;

Shinkura, Reiko ;

Honjo, Tasuku .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (01) :731-742

[5] Further evidence for involvement of a noncanonical function of uracil DNA glycosylase in class switch recombination [J].

Begum, Nasim A. ;

Stanlie, Andre ;

Doi, Tomomitsu ;

Sasaki, Yoko ;

Jin, Hai Wei ;

Kim, Yong Sung ;

Nagaoka, Hitoshi ;

Honjo, Tasuku .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (08) :2752-2757

[6] Biochemical analysis of hypermutational targeting by wild type and mutant activation-induced cytidine deaminase [J].

Bransteitter, R ;

Pham, P ;

Calabrese, P ;

Goodman, MF .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (49) :51612-51621

[7] Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase [J].

Bransteitter, R ;

Pham, P ;

Scharff, MD ;

Goodman, MF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :4102-4107

[8] LIGHT CHAIN GENE CONVERSION CONTINUES AT HIGH-RATE IN AN ALV-INDUCED CELL-LINE [J].

BUERSTEDDE, JM ;

REYNAUD, CA ;

HUMPHRIES, EH ;

OLSON, W ;

EWERT, DL ;

WEILL, JC .

EMBO JOURNAL, 1990, 9 (03) :921-927

[9] Transcription-targeted DNA deamination by the AID antibody diversification enzyme [J].

Chaudhuri, J ;

Tian, M ;

Khuong, C ;

Chua, K ;

Pinaud, E ;

Alt, FW .

NATURE, 2003, 422 (6933) :726-730

[10] DNA polymerase η is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse [J].

Delbos, Frederic ;

Aoufouchi, Said ;

Faili, Ahmad ;

Weill, Jean-Claude ;

Reynaud, Claude-Agnes .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (01) :17-23

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