ArabidopsisRETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control.
The rapidly proliferating cells in plant meristems must be protected from genome damage. Here, we show that the regulatory role of theArabidopsisRETINOBLASTOMA 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 interactin vitroandin plantaGenetic interaction between the RBR-silencedamiRBRandAtbrca1mutants 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.
School of Biological Sciences, Centre for Systems and Synthetic Biology, Royal Holloway, University of London, Egham, UK beatrix.horvath@rhul.ac.uk ben.scheres@wur.nl.|Department of Molecular Genetics, Utrecht University, Utrecht, The Netherlands.
Beatrix M
0000-0002-6083-992X
BM
Horvath
Institute of Microbiology CAS, v.v.i., Laboratory of Cell Reproduction, Prague 4, Czech Republic.
Hana
H
Kourova
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
Szilvia
S
Nagy
School of Biological Sciences, Centre for Systems and Synthetic Biology, Royal Holloway, University of London, Egham, UK.
Edit
0000-0002-9233-0773
E
Nemeth
Institute of Plant Biology, Biological Research Centre, Szeged, Hungary.
Zoltan
Z
Magyar
School of Biological Sciences, Centre for Systems and Synthetic Biology, Royal Holloway, University of London, Egham, UK.
Csaba
0000-0003-0640-6098
C
Papdi
School of Biological Sciences, Centre for Systems and Synthetic Biology, Royal Holloway, University of London, Egham, UK.
Zaki
0000-0002-0258-704X
Z
Ahmad
Department of Plant Sciences, Wageningen University Research Centre, Wageningen, The Netherlands.
Gabino F
GF
Sanchez-Perez
Department of Plant Sciences, Wageningen University Research Centre, Wageningen, The Netherlands.
Serena
S
Perilli
Department of Plant Sciences, Wageningen University Research Centre, Wageningen, The Netherlands.
Ikram
I
Blilou
Institute of Plant Biology, Biological Research Centre, Szeged, Hungary.
Aladár
A
Pettkó-Szandtner
Laboratory of Proteomic Research, Biological Research Centre, Szeged, Hungary.
Zsuzsanna
Z
Darula
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.|Technical Analytical Research Group of HAS, Budapest, Hungary.
Tamas
T
Meszaros
Institute of Microbiology CAS, v.v.i., Laboratory of Cell Reproduction, Prague 4, Czech Republic.
Pavla
P
Binarova
School of Biological Sciences, Centre for Systems and Synthetic Biology, Royal Holloway, University of London, Egham, UK.
Laszlo
L
Bogre
Department of Molecular Genetics, Utrecht University, Utrecht, The Netherlands beatrix.horvath@rhul.ac.uk ben.scheres@wur.nl.|Department of Plant Sciences, Wageningen University Research Centre, Wageningen, The Netherlands.
Ben
0000-0001-5400-9578
B
Scheres
D017360:Arabidopsis / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D004249:DNA Damage; D004260:DNA Repair; D018744:DNA, Plant / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism*; D018506:Gene Expression Regulation, Plant
C576589:ATM protein, Arabidopsis; D029681:Arabidopsis Proteins; D018744:DNA, Plant; D050684:E2F Transcription Factors; C496141:E2Fa protein, Arabidopsis; C487568:RBR1 protein, Arabidopsis; C576892:ATR protein, Arabidopsis; D064007:Ataxia Telangiectasia Mutated Proteins

Arabidopsis
; 
RETINOBLASTOMA RELATED
; BRCA1; DNA damage response; E2FA