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

Beatrix M. 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1261-1278
Number of pages18
JournalEMBO Journal
Issue number9
StatePublished - May 2 2017
Externally publishedYes

Bibliographical note

Funding Information:
We thank Charles White, Simon Amiard (Clermont Université, France), Oliver Trapp, Holger Puchta (Institute of Technology, Karlsruhe, Germany), Alfredo Cruz-Ramirez (Laboratorio Nacional de Genomica para la Biodiversidad, Cinvestav Sede Irapuato, Mexico), Ann Britt (University of California, at Davis, USA), Jim Murray, Walter Dewitte (Cardiff School of Biosciences, Cardiff University, Wales, UK), Wenkun Zhou (Wageningen University, The Netherlands) for sharing material; Christian Bachem (Wageningen University, The Netherlands) and Arp Schnittger (Hamburg University, Germany) for critically reading the manuscript; Laszlo Bako and Pal Miskolci (Umeå University, Sweden) for technical advice in ChIP technology, Kinga Bachem (Wageningen University, The Netherlands) for illustration and Milian Bachem (University of Rotterdam, The Netherlands) for statistical analysis. B.M.H was funded by a Marie-Curie IEF fellowship (FP7-PEOPLE-2012-IEF 330789), and by the Netherlands Organization for Scientific Research, Spinoza grant to B.S. G.S-P. was funded by the Utrecht University Focus & Mass grant and CBSG2/NCSB. Cs.P. was funded by a Marie-Curie IEF fellowship (FP7-PEOPLE-2012-IEF 330713) and both, Cs.P and L.B. by the BBSRC-NSF grant (BB/M025047/1). P.B. was funded by Grant Agency of the Czech Republic 15-11657S P501. Z.M. and E.N. were funded by the Hungarian Academy, OTKA 107838 and with Campus Hungary, TÁMOP-4.2.4B/2-11/1-2012-0001 fellowship, respectively. Z. M. and A.P-Sz. were supported by the grants GINOP-2.3.2-15-2016-00001 and Zs.D. by GINOP-2.3.2-15-2016-00032 and GINOP-2.3.2-15-2016-00020 from the Ministry for National Economy (Hungary). A.P-Sz. was funded by János Bolyai Research Scholarship of the Hungarian Academy of Sciences. S.P. was funded by ERA-CAPS grant 2013/15548/ALW. The funders had no role in the design of the study, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2017 The Authors. Published under the terms of the CC BY 4.0 license


  • Arabidopsis
  • BRCA1
  • DNA damage response
  • E2FA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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