Distinct DNA sequence and structure requirements for the two steps of V(D)J recombination signal cleavage

被引:148
作者
Ramsden, DA [1 ]
McBlane, JF [1 ]
vanGent, DC [1 ]
Gellert, M [1 ]
机构
[1] NIDDKD,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892
关键词
DNA double strand breaks; DNA hairpins; DNA unpairing; RAG1; RAG2;
D O I
10.1002/j.1460-2075.1996.tb00682.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cleavage of V(D)J recombination signals by purified RAG1 and RAG2 proteins permits the dissection of DNA structure and sequence requirements, The two recognition elements of a signal (nonamer and heptamer) are used differently, and their cooperation depends on correct helical phasing. The nonamer is most important for initial binding, while efficient nicking and hairpin formation require the heptamer sequence, Both nicking and hairpin formation are remarkably tolerant of variations in DNA structure, Certain flanking sequences inhibit hairpin formation, but this can be bypassed by base unpairing, and even a completely single-stranded signal sequence is well utilized, We suggest that DNA unpairing around the signal-coding border is essential for the initiation of V(D)J recombination.
引用
收藏
页码:3197 / 3206
页数:10
相关论文
共 32 条
[1]  
BOUBNOV NV, 1993, NUCLEIC ACIDS RES, V23, P1060
[2]   ISOLATION OF POINT MUTATIONS IN BACTERIOPHAGE MU ATTACHMENT REGIONS CLONED IN A LAMBDA-MINI-MU PHAGE [J].
BURLINGAME, RP ;
OBUKOWICZ, MG ;
LYNN, DL ;
HOWE, MM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (16) :6012-6016
[3]   CORRELATION OF LAC OPERATOR DNA IMINO PROTON-EXCHANGE KINETICS WITH ITS FUNCTION [J].
CHEUNG, S ;
ARNDT, K ;
LU, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (12) :3665-3669
[4]   ANALYSIS OF REGIONS OF RAG-2 IMPORTANT FOR V(D)J RECOMBINATION [J].
CUOMO, CA ;
OETTINGER, MA .
NUCLEIC ACIDS RESEARCH, 1994, 22 (10) :1810-1814
[5]  
EZEKIEL UR, 1995, IMMUNITY, V2, P381, DOI 10.1016/1074-7613(95)90146-9
[6]  
GELLERT M, 1992, ANNU REV GENET, V22, P425
[7]   CODING END SEQUENCE CAN MARKEDLY AFFECT THE INITIATION OF V(D)J RECOMBINATION [J].
GERSTEIN, RM ;
LIEBER, MR .
GENES & DEVELOPMENT, 1993, 7 (7B) :1459-1469
[8]   V(D)J RECOMBINATION - A FUNCTIONAL DEFINITION OF THE JOINING SIGNALS [J].
HESSE, JE ;
LIEBER, MR ;
MIZUUCHI, K ;
GELLERT, M .
GENES & DEVELOPMENT, 1989, 3 (07) :1053-1061
[9]   RECOMBINATION BETWEEN AN EXPRESSED IMMUNOGLOBULIN HEAVY-CHAIN GENE AND A GERMLINE VARIABLE GENE SEGMENT IN A LY-1+ B-CELL LYMPHOMA [J].
KLEINFIELD, R ;
HARDY, RR ;
TARLINTON, D ;
DANGL, J ;
HERZENBERG, LA ;
WEIGERT, M .
NATURE, 1986, 322 (6082) :843-846
[10]   SUBSTRATE-SPECIFICITY OF RECOMBINANT HUMAN-IMMUNODEFICIENCY-VIRUS INTEGRASE PROTEIN [J].
LAFEMINA, RL ;
CALLAHAN, PL ;
CORDINGLEY, MG .
JOURNAL OF VIROLOGY, 1991, 65 (10) :5624-5630