RAG1 and RAG2 in V(D)J recombination and transposition

被引:24
作者
Fugmann, SD [1 ]
机构
[1] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
关键词
RAG1; RAG2; V(D)J recombination; transposition; transposase; adaptive immune system;
D O I
10.1385/IR:23:1:23
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
RAGI and RAG2 are the key components of the V(D)J recombinase machinery that catalyses the somatic gene rearrangements of antigen receptor genes during lymphocyte development. In the first step of V(D)J recombination - DNA cleavage - the RAG proteins act together as an endonuclease to excise the DNA between two individual gene segments. They are also thought to be involved in the subsequent DNA joining step. In vitro, the RAG proteins catalyze the integration of the excised DNA element into target DNA completing a process similar to bacterial transposition. In vivo, this reaction is suppressed by an unknown mechanism. The individual roles of RAG1 and RAG2 in V(D)J recombination and transposition reactions are discussed based on mutation analyses and structure predictions.
引用
收藏
页码:23 / 39
页数:17
相关论文
共 103 条
[31]   MICE LACKING TDT - MATURE ANIMALS WITH AN IMMATURE LYMPHOCYTE REPERTOIRE [J].
GILFILLAN, S ;
DIERICH, A ;
LEMEUR, M ;
BENOIST, C ;
MATHIS, D .
SCIENCE, 1993, 261 (5125) :1175-1178
[32]   Nucleosome structure completely inhibits in vitro cleavage by the V(D)J recombinase [J].
Golding, A ;
Chandler, S ;
Ballestar, E ;
Wolffe, AP ;
Schlissel, MS .
EMBO JOURNAL, 1999, 18 (13) :3712-3723
[33]   Mutations in conserved regions of the predicted RAG2 kelch repeats block initiation of V(D)J recombination and result in primary immunodeficiencies [J].
Gomez, CA ;
Ptaszek, LM ;
Villa, A ;
Bozzi, F ;
Sobacchi, C ;
Brooks, EG ;
Notarangelo, LD ;
Spanopoulou, E ;
Pan, ZQ ;
Vezzoni, P ;
Cortes, P ;
Santagata, S .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (15) :5653-5664
[34]   DOWN-REGULATION OF RAG1 AND RAG2 GENE-EXPRESSION IN PREB CELLS AFTER FUNCTIONAL IMMUNOGLOBULIN HEAVY-CHAIN REARRANGEMENT [J].
GRAWUNDER, U ;
LEU, TMJ ;
SCHATZ, DG ;
WERNER, A ;
ROLINK, AG ;
MELCHERS, F ;
WINKLER, TH .
IMMUNITY, 1995, 3 (05) :601-608
[35]   Cell-cycle regulation of mammalian DNA double-strand-break repair [J].
Hendrickson, EA .
AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (04) :795-800
[36]  
HESSLEIN DG, 2001, IN PRESS ADV IMMUNOL
[37]   DNA transposition by the RAG1 and RAG2 proteins: A possible source of oncogenic translocations [J].
Hiom, K ;
Melek, M ;
Gellert, M .
CELL, 1998, 94 (04) :463-470
[38]   A stable RAG1-RAG2-DNA complex that is active in V(D)J Cleavage [J].
Hiom, K ;
Gellert, M .
CELL, 1997, 88 (01) :65-72
[39]   Assembly of a 12/23 paired signal complex: A critical control point in V(D)J recombination [J].
Hiom, K ;
Gellert, M .
MOLECULAR CELL, 1998, 1 (07) :1011-1019
[40]   NOVEL THIOETHER BOND REVEALED BY A 1.7-A CRYSTAL-STRUCTURE OF GALACTOSE-OXIDASE [J].
ITO, N ;
PHILLIPS, SEV ;
STEVENS, C ;
OGEL, ZB ;
MCPHERSON, MJ ;
KEEN, JN ;
YADAV, KDS ;
KNOWLES, PF .
NATURE, 1991, 350 (6313) :87-90