Horvath Beatrix M, Kourova Hana, Nagy Szilvia, Nemeth Edit, Magyar Zoltan, Papdi Csaba, Ahmad Zaki, Sanchez-Perez Gabino F, Perilli Serena, Blilou Ikram, Pettkó-Szandtner Aladár, Darula Zsuzsanna, Meszaros Tamas, Binarova Pavla, Bogre Laszlo, Scheres Ben
School of Biological Sciences, Centre for Systems and Synthetic Biology, Royal Holloway, University of London, Egham, UK
Department of Molecular Genetics, Utrecht University, Utrecht, The Netherlands.
EMBO J. 2017 May 2;36(9):1261-1278. doi: 10.15252/embj.201694561. Epub 2017 Mar 20.
The rapidly proliferating cells in plant meristems must be protected from genome damage. Here, we show that the regulatory role of the 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 and Genetic interaction between the RBR-silenced and 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.
植物分生组织中快速增殖的细胞必须受到保护，以免基因组受损。在此，我们表明，视网膜母细胞瘤相关蛋白（RBR）在细胞增殖中的调节作用可与保护基因组完整性的新功能相分离。DNA损伤时，RBR及其结合伴侣E2FA以依赖ATM和ATR的方式被招募到异染色质γH2AX标记的DNA损伤位点。这些γH2AX标记的DNA损伤区域被保守的修复蛋白AtBRCA1更分散地占据，AtBRCA1也可与RBR位点共定位。RBR与AtBRCA1存在物理相互作用，RBR沉默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。RBR与E2FA一起，直接参与转录性DNA损伤反应以及独立于p53的植物功能类似物SOG1的细胞死亡途径。因此，主要哺乳动物肿瘤抑制蛋白的植物同源物和类似物形成了一个调节网络，该网络协调细胞增殖与细胞及基因组完整性。
