Immunoglobulin diversification in DT40: a model for vertebrate DNA damage tolerance

被引：29
作者：
Sale, JE [1 ]
机构：
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
来源：
DNA REPAIR | 2004年 / 3卷 / 07期
关键词：
homologous recombination; translesion synthesis; gene conversions; immunoglobulin; DT40;
D O I：
10.1016/j.dnarep.2004.03.042
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Studies of recombination in vertebrates have rather lagged behind those in yeast and bacteria in large part due to the relative genetic intractability of vertebrate model systems. Immunoglobulin diversification in the chicken cell line DT40 provides a powerful combination of a physiological recombination process coupled with facile genetic modification. The immunoglobulin variable regions of DT40 constitutively diversify by a combination of gene conversion, in which sequence changes are templated from one of a number of upstream pseudogenes or by non-templated point mutation. Both of these events are initiated by abasic sites in the variable region DNA generated following the targeted deamination of cytidine by activation induced deaminase. Recent work has shown that the two outcomes, gene conversion and somatic mutation, are likely to reflect alternate pathways for the processing of these abasic sites. In this review I will discuss the current data on avian Ig gene diversification and examine how the immunoglobulin loci of DT40 may provide a useful model system for Studying the mechanisms and interactions of vertebrate recombination and pathways of DNA damage tolerance. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码：693 / 702
页数：10
相关论文
共 93 条
[21]   Evidence that a single replication fork proceeds from early to late replicating domains in the IgH locus in a non-B cell line [J].
Ermakova, OV ;
Nguyen, LH ;
Little, RD ;
Chevillard, C ;
Riblet, R ;
Ashouian, N ;
Birshtein, BK ;
Schildkraut, CL .
MOLECULAR CELL, 1999, 3 (03) :321-330
[22]   Recombinational repair of gaps in DNA is asymmetric in Ustilago maydis and can be explained by a migrating D-loop model [J].
Ferguson, DO ;
Holloman, WK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (11) :5419-5424
[23]   Mismatch repair deficiency interferes with the accumulation of mutations in chronically stimulated B cells and not with the hypermutation process [J].
Frey, S ;
Bertocci, B ;
Delbos, F ;
Quint, L ;
Weill, JC ;
Reynaud, CA .
IMMUNITY, 1998, 9 (01) :127-134
[24]   Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells [J].
Fujimori, A ;
Tachiiri, S ;
Sonoda, E ;
Thompson, LH ;
Dhar, PK ;
Hiraoka, M ;
Takeda, S ;
Zhang, Y ;
Reth, M ;
Takata, M .
EMBO JOURNAL, 2001, 20 (19) :5513-5520
[25]   A CHINESE-HAMSTER OVARY CELL-LINE HYPERSENSITIVE TO IONIZING-RADIATION AND DEFICIENT IN REPAIR REPLICATION [J].
FULLER, LF ;
PAINTER, RB .
MUTATION RESEARCH, 1988, 193 (02) :109-121
[26]   Coping with replication 'train wrecks' in Escherichia coli using Pol V, Pol II and RecA proteins [J].
Goodman, MF .
TRENDS IN BIOCHEMICAL SCIENCES, 2000, 25 (04) :189-195
[27]   Endogenous DNA abasic sites cause cell death in the absence of Apn1, Apn2 and Rad1/Rad10 in Saccharomyces cerevisiae [J].
Guillet, M ;
Boiteux, S .
EMBO JOURNAL, 2002, 21 (11) :2833-2841
[28]   Roles of yeast DNA polymerases δ and ζ and of Rev1 in the bypass of abasic sites [J].
Haracska, L ;
Unk, I ;
Johnson, RE ;
Johansson, E ;
Burgers, PMJ ;
Prakash, S ;
Prakash, L .
GENES & DEVELOPMENT, 2001, 15 (08) :945-954
[29]   Epstein-Barr virus and the somatic hypermutation of immunoglobulin genes in Burkitt's lymphoma cells [J].
Harris, RS ;
Croom-Carter, DSG ;
Rickinson, AB ;
Neuberger, MS .
JOURNAL OF VIROLOGY, 2001, 75 (21) :10488-10492
[30]   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
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