Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota

被引:167
作者
Faili, A [1 ]
Aoufouchi, S [1 ]
Flatter, E [1 ]
Guéranger, Q [1 ]
Reynaud, CA [1 ]
Weill, JC [1 ]
机构
[1] Hop Necker Enfants Malad, INSERM, U373, F-75730 Paris 15, France
关键词
D O I
10.1038/nature01117
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Somatic hypermutation of immunoglobulin genes is a unique, targeted, adaptive process. While B cells are engaged in germinal centres in T-dependent responses, single base substitutions are introduced in the expressed V-H/V-L genes to allow the selection of mutants with a higher affinity for the immunizing antigen. Almost every possible DNA transaction has been proposed to explain this process, but each of these models includes an error-prone DNA synthesis step that introduces the mutations(1,2). The Y family of DNA polymerases(3)-pol eta, pol iota, pol kappa and rev1-are specialized for copying DNA lesions and have high rates of error when copying a normal DNA template(4,5). By performing gene inactivation in a Burkitt's lymphoma cell line inducible for hypermutation, we show here that somatic hypermutation is dependent on DNA polymerase iota.
引用
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页码:944 / 947
页数:5
相关论文
共 29 条
[1]   An immunoglobulin mutator that targets G center dot C base pairs [J].
Bachl, J ;
Wabl, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) :851-855
[2]   5′-Deoxyribose phosphate lyase activity of human DNA polymerase ι in vitro [J].
Bebenek, K ;
Tissier, A ;
Frank, EG ;
McDonald, JP ;
Prasad, R ;
Wilson, SH ;
Woodgate, R ;
Kunkel, TA .
SCIENCE, 2001, 291 (5511) :2156-2159
[3]   Induction of somatic mutation in a human B cell line in vitro [J].
Denepoux, S ;
Razanajaona, D ;
Blanchard, D ;
Meffre, G ;
Capra, JD ;
Banchereau, J ;
Lebecque, S .
IMMUNITY, 1997, 6 (01) :35-46
[4]   INACTIVATION OF THE MOUSE MSH2 GENE RESULTS IN MISMATCH REPAIR DEFICIENCY, METHYLATION TOLERANCE, HYPERRECOMBINATION, AND PREDISPOSITION TO CANCER [J].
DEWIND, N ;
DEKKER, M ;
BERNS, A ;
RADMAN, M ;
RIELE, HT .
CELL, 1995, 82 (02) :321-330
[5]   Decreased frequency of somatic hypermutation and impaired affinity maturation but intact germinal center formation in mice expressing antisense RNA to DNA polymerase ζ [J].
Diaz, M ;
Verkoczy, LK ;
Flajnik, MF ;
Klinman, NR .
JOURNAL OF IMMUNOLOGY, 2001, 167 (01) :327-335
[6]   Analysis of the targeting of the hypermutational machinery and the impact of subsequent selection on the distribution of nucleotide changes in human VHDJH rearrangements [J].
Dorner, T ;
Foster, SJ ;
Brezinschek, HP ;
Lipsky, PE .
IMMUNOLOGICAL REVIEWS, 1998, 162 :161-171
[7]   AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line [J].
Faili, A ;
Aoufouchi, S ;
Guéranger, Q ;
Zober, C ;
Léon, A ;
Bertocci, B ;
Weill, JC ;
Reynaud, CA .
NATURE IMMUNOLOGY, 2002, 3 (09) :815-821
[8]   Altered nucleotide misinsertion fidelity associated with polι-dependent replication at the end of a DNA template [J].
Frank, EG ;
Tissier, A ;
McDonald, JP ;
Rapic-Otrin, V ;
Zeng, XM ;
Gearhart, PJ ;
Woodgate, R .
EMBO JOURNAL, 2001, 20 (11) :2914-2922
[9]   Molecular biology - Specialized DNA polymerases, cellular survival, and the genesis of mutations [J].
Friedberg, EC ;
Wagner, R ;
Radman, M .
SCIENCE, 2002, 296 (5573) :1627-1630
[10]   Emerging links between hypermutation of antibody genes and DNA polymerases [J].
Gearhart, PJ ;
Wood, RD .
NATURE REVIEWS IMMUNOLOGY, 2001, 1 (03) :187-192