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RESEARCH PAPER
1 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; 2 Department of Plant Biology, University of Geneva, Science III, CH-1211, Geneva 4, Switzerland; 3 Department of Stress and Developmental Biology, Institute of Plant Biochemistry, 06120 Halle/Saale, Germany; 4 Institute of Experimental Botany, 160 00, Praha 6, Czech Republic; 5 Department of Botany, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan; 6 Department of Integrated Genetics, National Institute of Genetics, Shizuoka 411-8540, Japan; 7 National Institute of Genetics, Japan Science and Technology Agency, PRESTO, Mishima, Shizuoka 411-8540, Japan
DNA repair associated with DNA replication is important for the conservation of genomic sequence information, whereas reconstitution of chromatin after replication sustains epigenetic information. We have isolated and characterized mutations in the BRU1 gene of Arabidopsis that suggest a novel link between these underlying maintenance mechanisms. Bru1 plants are highly sensitive to genotoxic stress and show stochastic release of transcriptional gene silencing. They also show increased intrachromosomal homologous recombination and constitutively activated expression of poly (ADP-ribose) polymerase-2 (AtPARP-2), the induction of which is associated with elevated DNA damage. Bru1 mutations affect the stability of heterochromatin organization but do not interfere with genome-wide DNA methylation. BRU1 encodes a novel nuclear protein with two predicted protein–protein interaction domains. The developmental abnormalities characteristic of bru1 mutant plants resemble those triggered by mutations in genes encoding subunits of chromatin assembly factor (CAF-1), the condensin complex, or MRE11. Comparison of bru1 with these mutants indicates cooperative roles in the replication and stabilization of chromatin structure, providing a novel link between chromatin replication, epigenetic inheritance, S-phase DNA damage checkpoints, and the regulation of meristem development.
[Keywords: Arabidopsis thaliana; DNA repair; epigenetic inheritance; gene silencing; homologous recombination]
Received December 18, 2003; revised version accepted March 3, 2004.
8 These authors contributed equally to this work.
12 E-MAIL shin.takeda{at}bioveg.unige.ch; FAX 41-22-3793107.
9 Present address: Institute of Plant Sciences, University of Bern, Altenbergrain 21, CH-3013 Bern, Switzerland
10 Present address: Department of Botany and Plant Pathology, Purdue University, West Lafayette, ID 47907-2054, USA
11 Present address: Gregor Mendel-Institute for Molecular Plant Biology, c/o University of Agricultural Sciences, Vienna, Muthgasse 18, A-1190 Vienna, Austria.
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