The retinoblastoma homolog RBR1 mediates localization of the repair protein RAD51 to DNA lesions in Arabidopsis.
The retinoblastoma homolog RBR1 mediates localization of the repair protein RAD51 to DNA lesions in Arabidopsis.
复制标题
DOI：
10.15252/embj.201694571
复制
发表时间：
2017-05-02
期刊：
影响因子：
--
通讯作者：
Schnittger A
中科院分区：
文献类型：
--
作者：
Biedermann S;Harashima H;Chen P;Heese M;Bouyer D;Sofroni K;Schnittger A
视网膜母细胞瘤蛋白（Rb）通常作为E2F调控基因的转录抑制因子，代表细胞周期的主要控制中心。在这里，我们表明，拟南芥Rb同系物视网膜母细胞瘤相关1（RBR1）的损失导致细胞死亡，特别是在暴露于遗传毒性药物，如环境毒素铝。虽然细胞死亡可以通过降低细胞增殖率来抑制，但rbr 1突变细胞表现出DNA损伤水平升高，表明RBR1在DNA损伤反应（DDR）中的直接作用。与其作为转录抑制因子的作用一致，我们发现RBR1直接结合并抑制关键的DDR基因，如辐射敏感51（RAD 51），这使得人们不清楚为什么rbr 1突变体对DNA损伤超敏感。然而，我们发现RBR1也需要RAD51定位到DNA损伤。我们进一步表明，RBR1本身以CDKB1活性依赖性方式靶向DNA断裂位点，并在损伤位点与RAD 51部分共定位。总之，这些结果暗示RBR1除了作为转录调节因子的典型功能外，还参与DNA结合修复复合物的组装。
The retinoblastoma protein (Rb), which typically functions as a transcriptional repressor of E2F‐regulated genes, represents a major control hub of the cell cycle. Here, we show that loss of the Arabidopsis Rb homolog RETINOBLASTOMA‐RELATED 1 (RBR1) leads to cell death, especially upon exposure to genotoxic drugs such as the environmental toxin aluminum. While cell death can be suppressed by reduced cell‐proliferation rates, rbr1 mutant cells exhibit elevated levels of DNA lesions, indicating a direct role of RBR1 in the DNA‐damage response (DDR). Consistent with its role as a transcriptional repressor, we find that RBR1 directly binds to and represses key DDR genes such as RADIATION SENSITIVE 51 (RAD51), leaving it unclear why rbr1 mutants are hypersensitive to DNA damage. However, we find that RBR1 is also required for RAD51 localization to DNA lesions. We further show that RBR1 is itself targeted to DNA break sites in a CDKB1 activity‐dependent manner and partially co‐localizes with RAD51 at damage sites. Taken together, these results implicate RBR1 in the assembly of DNA‐bound repair complexes, in addition to its canonical function as a transcriptional regulator.