Reduced X-ray resistance and homologous recombination frequencies in a RAD54(-/-) mutant of the chicken DT40 cell line

被引：236
作者：
Bezzubova, O [1 ]
Silbergleit, A [1 ]
YamaguchiIwai, Y [1 ]
Takeda, S [1 ]
Buerstedde, JM [1 ]
机构：
[1] KYOTO UNIV, SCH MED, BAYER CHAIR DEPT MOL IMMUNOL, KYOTO 606, JAPAN
来源：
CELL | 1997年 / 89卷 / 02期
关键词：
D O I：
10.1016/S0092-8674(00)80198-1
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：
rad54 mutants of the yeast Saccharomyces cerevisiae are extremely X-ray sensitive and have decreased mitotic recombination frequencies because of a defect in double-strand break repair. A RAD54 homolog was disrupted in the chicken B cell line DT40, which undergoes immunoglobulin gene conversion and exhibits unusually high ratios of targeted to random integration after DNA transfection. Homozygous RAD54(-/-) mutant clones were highly X-ray sensitive compared to wildtype cells. The rate of immunoglobulin gene conversion was 6- to 8-fold reduced, and the frequency of targeted integration was at least two orders of magnitude decreased in the mutant clones. Reexpression of the RAD54 cDNA restored radiation resistance and targeted integration activity. The reported phenotype provides the first genetic evidence of a link between double-strand break repair and homologous recombination in vertebrate cells.
引用
收藏
页码：185 / 193
页数：9
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