BRU1, a novel link between responses to DNA damage and epigenetic gene silencing in Arabidopsis.
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.
Takeda
Shin
S
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. shin.takeda@bioveg.unige.ch
Tadele
Zerihun
Z
Hofmann
Ingo
I
Probst
Aline V
AV
Angelis
Karel J
KJ
Kaya
Hidetaka
H
Araki
Takashi
T
Mengiste
Tesfaye
T
Mittelsten Scheid
Ortrun
O
Shibahara
Kei-ichi
K
Scheel
Dierk
D
Paszkowski
Jerzy
J
D017360:Arabidopsis / Q000235:genetics* / Q000254:growth & development; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D020552:Comet Assay; D004249:DNA Damage; D019175:DNA Methylation; D004261:DNA Replication; D018744:DNA, Plant / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D018506:Gene Expression Regulation, Plant; D020868:Gene Silencing; D017343:Genes, Plant / Q000502:physiology*; D006570:Heterochromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D018519:Meristem / Q000254:growth & development; D009154:Mutation / Q000235:genetics; D030821:Plants, Genetically Modified; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D018744:DNA, Plant; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae