The RAD51 protein supports homologous recombination by an exchange mechanism in mammalian cells

被引:61
作者
Arnaudeau, C [1 ]
Helleday, T [1 ]
Jenssen, D [1 ]
机构
[1] Stockholm Univ, Wallenberg Lab, Dept Genet & Cellular Toxicol, S-10691 Stockholm, Sweden
关键词
RAD51; mammalian cells; homologous recombination; exchange mechanism; hypoxanthine-guanine phosphoribosyltransferase;
D O I
10.1006/jmbi.1999.2856
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
information concerning the function of recombination proteins in mammalian cells has been obtained from biochemical studies, but little is known about their mechanisms of action in growing cells. The eukaryotic recombination protein RAD51, a homologue of the Escherichia coli RecA protein, has been shown to interact with various proteins, including the p53 protein, the guardian of genomic stability maintenance. Here, the hamster RAD51 protein, CgRAD51, has been overexpressed in the SPD8 cell line, derived from Chinese hamster V79 cells. This cell line offers unique possibilities for studying different mechanisms for homologous recombination on endogenous substrates. We report that the SPD8 cell line contains a mutated p53 gene, which provides new insights into the recombination process in these cells. The present study demonstrates that overexpression of CgRAD51 in these cells results in a two- to threefold increase in endogenous recombination. In addition, sequence analysis indicated that RAD51 promotes homologous recombination by a chromatid exchange mechanism. (C) 1999 Academic Press.
引用
收藏
页码:1231 / 1238
页数:8
相关论文
共 47 条
[31]   Human Rad52 protein promotes single-strand DNA annealing followed by branch migration [J].
Reddy, G ;
Golub, EI ;
Radding, CM .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1997, 377 (01) :53-59
[32]   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
[33]   Association of BRCA1 with Rad51 in mitotic and meiotic cells [J].
Scully, R ;
Chen, JJ ;
Plug, A ;
Xiao, YH ;
Weaver, D ;
Feunteun, J ;
Ashley, T ;
Livingston, DM .
CELL, 1997, 88 (02) :265-275
[34]   Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2 [J].
Sharan, SK ;
Morimatsu, M ;
Albrecht, U ;
Lim, DS ;
Regel, E ;
Dinh, C ;
Sands, A ;
Eichele, G ;
Hasty, P ;
Bradley, A .
NATURE, 1997, 386 (6627) :804-810
[35]   CLONING OF HUMAN, MOUSE AND FISSION YEAST RECOMBINATION GENES HOMOLOGOUS TO RAD51 AND RECA [J].
SHINOHARA, A ;
OGAWA, H ;
MATSUDA, Y ;
USHIO, N ;
IKEO, K ;
OGAWA, T .
NATURE GENETICS, 1993, 4 (03) :239-243
[36]   RAD51 PROTEIN INVOLVED IN REPAIR AND RECOMBINATION IN SACCHAROMYCES-CEREVISIAE IS A RECA-LIKE PROTEIN [J].
SHINOHARA, A ;
OGAWA, H ;
OGAWA, T .
CELL, 1992, 69 (03) :457-470
[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]   p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction [J].
Sturzbecher, HW ;
Donzelmann, B ;
Henning, W ;
Knippschild, U ;
Buchhop, S .
EMBO JOURNAL, 1996, 15 (08) :1992-2002
[39]  
SUGAWARA N, 1995, J TRACE ELEM EXP MED, V8, P1
[40]   CATALYSIS OF ATP-DEPENDENT HOMOLOGOUS DNA PAIRING AND STRAND EXCHANGE BY YEAST RAD51 PROTEIN [J].
SUNG, P .
SCIENCE, 1994, 265 (5176) :1241-1243