Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control. (20th March 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: EMBO journal. Volume 36:Number 9(2017)
• Page Start: 1261
• Page End: 1278
• Publication Date: 2017-03-20
• Subjects: Arabidopsis -- BRCA1 -- DNA damage response -- E2FA -- RETINOBLASTOMA RELATED; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201694561
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: 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. Synopsis: Arabidopsis RETINOBLASTOMA RELATED (RBR), the plant homolog of the mammalian retinoblastoma tumor suppressor protein, transcriptionally regulates damage response and cell death pathways, but also directly cooperates with the repair factor BRCA1 to maintain genome integrity after damage. Beyond its role in cell cycle control, RBR has a function in maintaining genome integrity and cell viability. RBR together with E2FA frequently accumulates on γH2AX‐labelled damage foci during DNA damage responses. RBR and AtBRCA1 physically interact and co‐localise on a subset of γH2AX‐labelled nuclear foci. Genetic interactions of RBR and AtBRCA1 support their synergistic action in DNA repair. RBR and E2FA regulate AtBRCA1 transcription and cell death responses in a SOG1‐independent pathway. Abstract : The tumor suppressor plant homolog transcriptionally regulates damage response and cell death pathways, but also directly cooperates with the repair factor BRCA1 to maintain genome integrity after damage.