A Conditional Mouse Model for Measuring the Frequency of Homologous Recombination Events In Vivo in the Absence of Essential Genes

被引:11
作者
Brown, Adam D. [1 ,2 ]
Claybon, Alison B. [2 ]
Bishop, Alexander J. R. [1 ,2 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA
[2] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA
关键词
RETINAL-PIGMENT EPITHELIUM; BLOOMS-SYNDROME GENE; STRAND BREAK REPAIR; EYED UNSTABLE MUTATION; SISTER-CHROMATID EXCHANGES; DNA-DAMAGE RESPONSE; CELL-CYCLE; OVARIAN-CANCER; SYNDROME HELICASE; TARGETED DISRUPTION;
D O I
10.1128/MCB.00848-10
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
The ability to detect and repair DNA damage is crucial to the prevention of various diseases. Loss of function of genes involved in these processes is known to result in significant developmental defects and/or predisposition to cancer. One such DNA repair mechanism, homologous recombination, has the capacity to repair a wide variety of lesions. Knockout mouse models of genes thought to be involved in DNA repair processes are frequently lethal, making in vivo studies very difficult, if not impossible. Therefore, we set out to develop an in vivo conditional mouse model system to facilitate investigations into the involvement of essential genes in homologous recombination. To test our model, we measured the frequency of spontaneous homologous recombination using the pink-eyed unstable mouse model, in which we conditionally excised either Blm or full-length Brca1 (breast cancer 1, early onset). These two genes are hypothesized to have opposing roles in homologous recombination. In summary, our in vivo data supports in vitro studies suggesting that BLM suppresses homologous recombination, while full-length BRCA1 promotes this process.
引用
收藏
页码:3593 / 3602
页数:10
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