Regulation of Rad51 Function by c-Abl in Response to DNA Damage*
Regulation of Rad51 Function by c-Abl in Response to DNA Damage*
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DOI：
10.1074/jbc.273.7.3799
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发表时间：
1998-02
期刊：
影响因子：
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通讯作者：
Zhi-Min Yuan;Yinyin Huang;T. Ishiko;S. Nakada;T. Utsugisawa;S. Kharbanda;Rong Wang;P. Sung;A. Shinohara;R. Weichselbaum;D. Kufe
中科院分区：
文献类型：
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作者：
Zhi-Min Yuan;Yinyin Huang;T. Ishiko;S. Nakada;T. Utsugisawa;S. Kharbanda;Rong Wang;P. Sung;A. Shinohara;R. Weichselbaum;D. Kufe
Rad 51蛋白是细菌RecA的同源物，在DNA双链断裂修复和遗传重组中发挥作用。而Rad 51催化同源DNA分子之间的ATP依赖性配对和链交换，这种功能的调节是未知的。c-Abl酪氨酸激酶被电离辐射和某些其他DNA损伤剂激活。在这里，我们证明了c-Abl与Rad 51组成性相互作用。我们表明c-Abl在体外磷酸化Tyr-54上的Rad 51。结果还显示，用电离辐射处理细胞诱导Rad 51的c-Abl依赖性磷酸化。c-Abl对Rad 51的磷酸化抑制了Rad 51与DNA的结合以及Rad 51在ATP依赖性DNA链交换反应中的功能。这些发现代表了Rad 51受磷酸化调节的第一个证明，并支持c-Abl在调节Rad 51依赖性重组中对DNA损伤的响应的功能作用。
The Rad51 protein, a homolog of bacterial RecA, functions in DNA double-strand break repair and genetic recombination. Whereas Rad51 catalyzes ATP-dependent pairing and strand exchange between homologous DNA molecules, regulation of this function is unknown. The c-Abl tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents. Here we demonstrate that c-Abl interacts constitutively with Rad51. We show that c-Abl phosphorylates Rad51 on Tyr-54 in vitro. The results also show that treatment of cells with ionizing radiation induces c-Abl-dependent phosphorylation of Rad51. Phosphorylation of Rad51 by c-Abl inhibits the binding of Rad51 to DNA and the function of Rad51 in ATP-dependent DNA strand exchange reactions. These findings represent the first demonstration that Rad51 is regulated by phosphorylation and support a functional role for c-Abl in regulating Rad51-dependent recombination in the response to DNA damage.