S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51
S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51
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DOI：
10.1182/blood-2002-01-0278
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发表时间：
2002-10-01
期刊：
影响因子：
20.3
通讯作者：
D'Andrea, AD
中科院分区：
文献类型：
--
作者：
Taniguchi, T;Garcia-Higuera, I;D'Andrea, AD
范可尼贫血（FA）是一种常染色体隐性遗传性癌症易感性疾病，其特征是细胞对丝裂霉素C的敏感性和细胞周期进展缺陷。六个FA基因（对应于亚型A，C，D2，E，F和G）已被克隆，编码的FA蛋白在一个共同的途径相互作用。DNA损伤激活这一途径，导致下游FANCD 2蛋白的单泛素化，并靶向含有BRCA 1的核灶。在目前的研究中，我们证明，FANCD 2也经历了单细胞液化在S期的细胞周期。Monoubiquitinated FANCD 2与BRCA 1和RAD 51共定位于S期特异性核灶中。FANCD 2的单泛素化是细胞暴露于丝裂霉素C后正常细胞周期进展所必需的。我们的数据表明FANCD 2的单泛素化是高度调节的，并且他们表明FANCD 2/BRCA 1复合物和FANCD 2/RAD 51复合物参与S期特异性细胞过程，例如通过同源重组的DNA修复。(C)2002年，美国血液学会。
Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and defective cell-cycle progression. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have been cloned, and the encoded FA proteins interact in a common pathway. DNA damage activates this pathway, leading to monoubiquitination of the downstream FANCD2 protein and targeting to nuclear foci containing BRCA1. In the current study, we demonstrate that FANCD2 also undergoes monoubliquitination during S phase of the cell cycle. Monoubiquitinated FANCD2 colocalizes with BRCA1 and RAD51 in S-phase-specific nuclear foci. Monoubiquitination of FANCD2 is required for normal cell-cycle progression following cellular exposure to mitomycin C. Our data indicate that the monoubiquitination of FANCD2 Is highly regulated, and they suggest that FANCD2/BRCA1 complexes and FANCD2/RAD51 complexes participate in an S-phase-specific cellular process, such as DNA repair by homologous recombination. (C) 2002 by The American Society of Hematology.