Jasmonates comprise a family of plant hormones that regulate gene expression to modulate diverse developmental and defensive processes. To screen a set of jasmonate-responsive Arabidopsis genes, we performed a microarray analysis using an Affymetrix GeneChip containing about 8,300 gene probes synthesized in situ. External treatment with 100 microM methyl jasmonate resulted in significant changes (more than twofold increases or decreases) in the expression levels of 137 genes in the rosette leaves of 5-week-old Arabidopsis plants. Of these, 74 genes were up-regulated, including those involved in jasmonate biosynthesis, defense responses, oxidative stress responses, senescence, and cell wall modification. In contrast, the expression of genes involved in chlorophyll constitution and photosynthesis was down-regulated. Most importantly, the jasmonate treatment significantly reduced transcripts of abscisic acid-responsive cold/drought-stress genes, which suggests that an antagonistic interaction occurs between the jasmonate and abscisic acid signaling pathways in abiotic stress responses. Northern blot analysis of some selected genes revealed that the jasmonate-responsive genes exhibited unique time-course expression patterns after the external jasmonate treatment. Based on the basic clustering of the genes, we established a likely regulation scenario: the genes induced early after treatment are involved in signaling mechanisms that activate or repress other genes, whereas intermediate- and late-accumulating genes are activated by the signaling mechanisms and are subsequently involved in the ultimate jasmonate-modulated cellular responses.

Chromosome number and structure instability is the hallmark of cancer. Equal chromosome segregation is guaranteed by the spindle assembly checkpoint (SAC), thus defective SAC leads to chromosome instability. However, aneuploidy alone is not oncogenic, and whether compromised SAC is associated with structure instability remains elusive. BubR1 is a core component of SAC, which is acetylated at lysine 250 in mitosis. Previously, we showed that deficiency of BubR1 acetylation in mice (K243R/+) leads to spontaneous tumorigenesis via chromosome mis-segregation. Here, we asked whether loss of BubR1 acetylation is associated with chromosome structure instability by examiningK243R/+mice intercrossed top53-deficient mice. Genome-wide sequencing and spectral karyotyping of the double mutant mouse tumors revealed that BubR1 acetylation deficiency leads to complex chromosome rearrangements, including Robertsonian-like whole-arm translocations and premature sister-chromatid separations (PMSCS). In primary MEFs, replication stress was markedly increased in telomeres and centromeres, suggesting that the replication stress underlies the significant increase of DNA damage and subsequent chromosome rearrangements. Furthermore, defects in BubR1 acetylation at K250 were detected in human cancers as well. Collectively, we propose that chromosome mis-segregation by the loss of BubR1 acetylation causes chromosome structure instability, leading to massive chromosome rearrangements through the induction of replication stress.

Accurate chromosomal segregation during mitosis is regulated by the spindle assembly checkpoint (SAC). SAC failure results in aneuploidy, a hallmark of cancer. However, many studies have suggested that aneuploidy alone is not oncogenic. We have reported that BubR1 acetylation deficiency in mice (K243R/+) caused spontaneous tumorigenesis via weakened SAC signaling and unstable chromosome‐spindle attachment, resulting in massive chromosomal mis‐segregation. In addition to aneuploidy, cells derived from K243R/+ mice exhibited moderate genetic instability and chromosomal translocation. Here, we investigated how the loss of BubR1 acetylation led to genetic instability and chromosomal rearrangement. To rescue all chromosomal abnormalities generated by the loss of BubR1 acetylation during development, K243R/+ mice were crossed with p53‐deficient mice. Genome‐wide sequencing and spectral karyotyping of tumors derived from these double‐mutant mice revealed that BubR1 acetylation deficiency was associated with complex chromosomal rearrangements, including Robertsonian‐like whole‐arm translocations. By analyzing the telomeres and centromeres in metaphase chromosome spreads, we found that BubR1 acetylation deficiency increased the collapse of stalled replication forks, commonly referred to as replication stress, and led to DNA damage and chromosomal rearrangements. BubR1 mutations that are critical in interacting with PCAF acetyltransferase and acetylating K250, L249F and A251P, were found from human cancers. Furthermore, a subset of human cancer cells exhibiting whole‐arm translocation also displayed defects in BubR1 acetylation, supporting that defects in BubR1 acetylation in mitosis contributes to tumorigenesis. Collectively, loss of BubR1 acetylation provokes replication stress, particularly at the telomeres, leading to genetic instability and chromosomal rearrangement.