DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes

被引:282
作者
Grawunder, U
Zimmer, D
Fugmann, S
Schwarz, K
Lieber, MR [1 ]
机构
[1] Univ So Calif, Sch Med, Norris Comprehens Canc Ctr, Dept Pathol, Los Angeles, CA 90033 USA
[2] Univ Ulm, Dept Transfus Med, D-89081 Ulm, Germany
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S1097-2765(00)80147-1
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
Nonhomologous DNA end joining (NHEJ) is the major pathway for repairing double-strand DNA breaks. V(D)J recombination is a double-strand DNA breakage and rejoining process that relies on NHEJ for the joining steps. Here we show that the targeted disruption of both DNA ligase IV alleles in a human pre-B cell line renders the cells sensitive to ionizing radiation and ablates V(D)J recombination. This phenotype can only be reversed by complementation with DNA ligase IV but not by expression of either of the remaining two ligases, DNA ligase I or III. Hence, DNA ligase IV is the activity responsible for the ligation step in NHEJ and in V(D)J recombination.
引用
收藏
页码:477 / 484
页数:8
相关论文
共 43 条
[31]   DNA ligase IV from HeLa cell nuclei [J].
Robins, P ;
Lindahl, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (39) :24257-24261
[32]   RAG-1 MUTATIONS THAT AFFECT THE TARGET SPECIFICITY OF V(D)J RECOMBINATION - A POSSIBLE DIRECT ROLE OF RAG-1 IN SITE RECOGNITION [J].
SADOFSKY, MJ ;
HESSE, JE ;
VANGENT, DC ;
GELLERT, M .
GENES & DEVELOPMENT, 1995, 9 (17) :2193-2199
[33]   DEFINITION OF A CORE REGION OF RAG-2 THAT IS FUNCTIONAL IN V(D)J RECOMBINATION [J].
SADOFSKY, MJ ;
HESSE, JE ;
GELLERT, M .
NUCLEIC ACIDS RESEARCH, 1994, 22 (10) :1805-1809
[34]   Repair of site-specific double-strand breaks in a mammalian chromosome by homologous and illegitimate recombination [J].
Sargent, RG ;
Brenneman, MA ;
Wilson, JH .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (01) :267-277
[35]   A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks [J].
Schar, P ;
Herrmann, G ;
Daly, G ;
Lindahl, T .
GENES & DEVELOPMENT, 1997, 11 (15) :1912-1924
[36]  
Schatz D G, 1997, Semin Immunol, V9, P149, DOI 10.1006/smim.1997.0068
[37]   Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death [J].
Sonoda, E ;
Sasaki, MS ;
Buerstedde, JM ;
Bezzubova, O ;
Shinohara, A ;
Ogawa, H ;
Takata, M ;
Yamaguchi-Iwai, Y ;
Takeda, S .
EMBO JOURNAL, 1998, 17 (02) :598-608
[38]   Identification of Saccharomyces cerevisiae DNA ligase .4. Involvement in DNA double-strand break repair [J].
Teo, SH ;
Jackson, SP .
EMBO JOURNAL, 1997, 16 (15) :4788-4795
[39]   Mammalian DNA ligases [J].
Tomkinson, AE ;
Levin, DS .
BIOESSAYS, 1997, 19 (10) :893-901
[40]  
WEI YF, 1995, MOL CELL BIOL, V15, P3206