Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control.
Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control.
复制标题
DOI：
10.15252/embj.201694561
复制
发表时间：
2017-05-02
期刊：
影响因子：
--
通讯作者：
Scheres B
中科院分区：
文献类型：
--
作者：
Horvath BM;Kourova H;Nagy S;Nemeth E;Magyar Z;Papdi C;Ahmad Z;Sanchez-Perez GF;Perilli S;Blilou I;Pettkó-Szandtner A;Darula Z;Meszaros T;Binarova P;Bogre L;Scheres B
必须保护植物分生组织中快速增殖的细胞免受基因组损伤。在这里，我们表明，拟南芥视网膜母细胞瘤相关基因（RBR）在细胞增殖中的调节作用，可以从一个新的功能，在维护基因组的完整性分开。在DNA损伤后，RBR及其结合伴侣E2FA以ATM和ATR依赖性方式被募集到异染色质γH2AX标记的DNA损伤灶。这些γH2AX标记的DNA损伤更分散地被保守的修复蛋白AtBRCA1占据，AtBRCA1也可以与RBR灶共定位。RBR和AtBRCA 1在体外和植物中物理相互作用。RBR沉默的amiRBR和Atbrca1突变体之间的遗传相互作用表明，RBR和AtBRCA1可能在维持基因组完整性方面共同发挥作用。与E2FA一起，RBR直接参与转录DNA损伤反应以及不依赖于p53的植物功能类似物SOG 1的细胞死亡途径。因此，植物同源物和类似物的主要哺乳动物肿瘤抑制蛋白形成一个调节网络，协调细胞增殖与细胞和基因组的完整性。
The rapidly proliferating cells in plant meristems must be protected from genome damage. Here, we show that the regulatory role of the Arabidopsis RETINOBLASTOMA RELATED (RBR) in cell proliferation can be separated from a novel function in safeguarding genome integrity. Upon DNA damage, RBR and its binding partner E2FA are recruited to heterochromatic γH2AX‐labelled DNA damage foci in an ATM‐ and ATR‐dependent manner. These γH2AX‐labelled DNA lesions are more dispersedly occupied by the conserved repair protein, AtBRCA1, which can also co‐localise with RBR foci. RBR and AtBRCA1 physically interact in vitro and in planta. Genetic interaction between the RBR‐silenced amiRBR and Atbrca1 mutants suggests that RBR and AtBRCA1 may function together in maintaining genome integrity. Together with E2FA, RBR is directly involved in the transcriptional DNA damage response as well as in the cell death pathway that is independent of SOG1, the plant functional analogue of p53. Thus, plant homologs and analogues of major mammalian tumour suppressor proteins form a regulatory network that coordinates cell proliferation with cell and genome integrity.