Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control

Beatrix Horvath, Hana Kourova, Szilvia Nagy, Edit Nemeth, Zoltan Magyar, Csaba Papdi, Zaki Ahmad, Gabino F. Sanchez-Perez, Serena Perilli, Ikram Blilou, Aladár Pettkó-Szandtner, Zsuzsanna Darula, Tamas Meszaros, Pavla Binarova, Laszlo Bogre, Ben Scheres

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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 ATRdependent 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.
Original languageEnglish
Pages (from-to)1261-1278
Number of pages18
JournalEMBO Journal
Volume36
Issue number9
Early online date20 Mar 2017
DOIs
Publication statusPublished - 2 May 2017

Keywords

  • Arabidopsis, BRCA1, DNA damage response, E2FA, RETINOBLASTOMA-RELATED

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