Cre-mediated recombination can induce apoptosis in vivo by activating the p53 DNA damage-induced pathway.
Cre-mediated recombination can induce apoptosis in vivo by activating the p53 DNA damage-induced pathway.
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DOI：
10.1002/dvg.20799
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发表时间：
2012-02
期刊：
影响因子：
1.5
通讯作者：
Mackem, Susan
中科院分区：
文献类型：
--
作者：
Zhu, Jianjian;Minh-Thanh Nguyen;Nakamura, Eiichiro;Yang, Junming;Mackem, Susan
Cre介导的细胞凋亡已在许多情况下在表达Cre重组酶的小鼠中观察到，并且可以混淆基因工程条件突变体或转基因等位基因的分析。已经提出了几种机制来解释这种现象。我们发现，诱导的细胞凋亡的程度大致与基因组中存在的loxP位点的拷贝数相关，并且即使只有几个loxP位点存在，也会伴随一定程度的细胞凋亡增加，如在条件性floxed等位基因中所发生的那样。在这种情况下，铬诱导的细胞凋亡是完全依赖于p53，这表明细胞凋亡是刺激p53激活响应于铬介导的重组过程中发生的DNA损伤。
Cre-mediated apoptosis has been observed in many contexts in mice expressing Cre-recombinase, and can confound the analysis of genetically engineered conditional mutant or transgenic alleles. Several mechanisms have been proposed to explain this phenomenon. We find that the degree of apoptosis induced correlates roughly with the copy number of loxP sites present in the genome and that some level of increased apoptosis accompanies the presence of even only a few loxP sites, as occurs in conditional floxed alleles. Cre-induced apoptosis in this context is completely p53-dependent, suggesting that the apoptosis is stimulated by p53 activation in response to DNA damage incurred during the process of Cre-mediated recombination.
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影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
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影响因子：
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