Xrcc3 is required for assembly of Rad51 complexes in vivo
Xrcc3 is required for assembly of Rad51 complexes in vivo
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DOI：
10.1074/jbc.273.34.21482
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发表时间：
1998-08-21
影响因子：
4.8
通讯作者：
Shinohara, A
中科院分区：
文献类型：
--
作者：
Bishop, DK;Ear, U;Shinohara, A
Rad51是与细菌重组修复蛋白RecA相关的真核蛋白家族的成员，Rad51蛋白定位于中国仓鼠卵巢细胞的多个亚核病灶。亚核Rad51病灶可由电离辐射或DNA交联剂顺铂诱导。这些病灶的形成可能反映了促进DNA修复的Rad51多聚体形式的组装。中国仓鼠卵巢细胞系irs1SF对DNA损伤剂敏感，不存在Rad51损伤灶的形成。irs1SF细胞的Rad51焦点形成缺陷通过编码修复蛋白Xrcc3的构建体得到纠正。Xrcc3是Rad51的人类同源物，先前因其能够纠正irs1SF细胞的辐射敏感性而被分离出来。Rad51蛋白稳态水平的变化不能解释irs1SF缺陷，也不能解释DNA损伤后灶的出现。这些结果表明，在DNA修复过程中，多聚体形式的Rad51的组装或稳定需要Xrcc3。DNA蛋白激酶两种不同组分缺陷的细胞系在损伤反应中形成Rad51病灶，表明DNA蛋白激酶不需要损伤诱导的Rad51动员。
Rad51 is a member of a family of eukaryotic proteins related to the bacterial recombinational repair protein RecA, Rad51 protein localizes to multiple subnuclear foci in Chinese hamster ovary cells. Subnuclear Rad51 foci are induced by ionizing radiation or the DNA crosslinking agent cisplatin. Formation of these foci is likely to reflect assembly of a multimeric form of Rad51 that promotes DNA repair. Formation of damage-induced Rad51 foci does not occur in the Chinese hamster ovary cell line irs1SF, which is sensitive to DNA damaging agents. The Rad51 focus formation defect of irs1SF cells is corrected by a construct that encodes the repair protein Xrcc3. Xrcc3 is a human homolog of Rad51 previously isolated by virtue of its ability to correct the radiation sensitivity of irs1SF cells. Changes in the steady state level of Rad51 protein do not account for the irs1SF defect nor do they account for the appearance of foci following DNA damage. These results suggest that Xrcc3 is required for the assembly or stabilization of a multimeric form of Rad51 during DNA repair. Cell Lines defective in two different components of DNA protein kinase formed Rad51 foci in response to damage, indicating DNA protein kinase is not required for damaged-induced mobilization of Rad51.