Abstract Repair of DNA double-strand breaks (DSBs) with homologous chromosomes is a hallmark of meiosis that is mediated by recombination ‘bridges’ between homolog axes. This process requires cooperation of DMC1 and RAD51 to promote homology search and strand exchange. The mechanism(s) regulating DMC1/RAD51-ssDNA nucleoprotein filament and the components of ‘bridges’ remain to be investigated. Here we show that MEIOK21 is a newly identified component of meiotic recombination bridges and is required for efficient formation of DMC1/RAD51 foci. MEIOK21 dynamically localizes on chromosomes from on-axis foci to ‘hanging foci’, then to ‘bridges’, and finally to ‘fused foci’ between homolog axes. Its chromosome localization depends on DSBs. Knockout of Meiok21 decreases the numbers of HSF2BP and DMC1/RAD51 foci, disrupting DSB repair, synapsis and crossover recombination and finally causing male infertility. Therefore, MEIOK21 is a novel recombination factor and probably mediates DMC1/RAD51 recruitment to ssDNA or their stability on chromosomes through physical interaction with HSF2BP.

Zingiberaceae is taxonomically complex family where species are perennial herb. However, lack of chloroplast genomic information severely hinders our understanding of Zingiberaceae species in the research of evolution and phylogenetic relationships. In this study, the complete chloroplast (cp) genomes of fourteen Curcuma species were assembled and characterized using next-generation sequencing. We compared the genome features, repeat sequences, sequence divergence, and constructed the phylogenetic relationships of the 25 Zingiberaceae species. In each Zingiberaceae species, the 25 complete chloroplast genomes ranging from 155,890 bp (Zingiber spectabile) to 164,101 bp (Lanxangia tsaoko) contained 111 genes consisting of 77 protein coding genes, 4 ribosomal RNAs and 30 transfer RNAs. These chloroplast genomes are similar to most angiosperm that consisted of a four-part circular DNA molecules. Moreover, the characteristics of the long repeats sequences and simple sequence repeats (SSRs) were found. Six divergent hotspots regions (matK-trnk, Rps16-trnQ, petN-psbM, rpl32, ndhA, and ycf1) were identified in the 25 Zingiberaceae chloroplast genomes, which could be potential molecular markers. In addition to Wurfbainia longiligularis, the ψycf1 was discovered among the 25 Zingiberaceae species. The shared protein coding genes from 52 Zingiberales plants and four other family species as out groups were used to construct phylogenetic trees distinguished by maximum parsimony (MP), maximum likelihood (ML) and Bayesian inference (BI) and showed that Musaceae was the basal group in Zingiberales, and Curcuma had a close relationship with Stahlianthu. Besides this, Curcuma flaviflora was clustered together with Zingiber. Its distribution area (Southeast Asia) overlaps with the latter. Maybe hybridization occur in related groups within the same region. This may explain

BackgroundMultiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells.Methodology/Principal FindingsMM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal cells (BMSCs) were treated with 6-OAP. The effects of 6-OAP plus other drugs on MM.1S cells were evaluated. The in vivo therapeutic efficacy and pharmacokinetic features of 6-OAP were tested in nude mice bearing U266 cells and Sprague-Dawley rats, respectively. We found that 6-OAP suppressed the proliferation of dexamethasone-sensitive and dexamethasone-resistant cell lines and primary CD138+ MM cells. 6-OAP caused mitotic arrest, accompanied by activation of spindle assembly checkpoint and blockage of ubiquitiniation and subsequent proteasomal degradation of cyclin B1. Combined use of 6-OAP and bortezomib induced potentiated cytotoxicity with inactivation of ERK1/2 and activation of JNK1/2 and Casp-8/-3. 6-OAP overcame the protective effects of IL-6 and IGF-I on MM cells through inhibition of Jak2/Stat3 and Akt, respectively. 6-OAP inhibited BMSCs-facilitated MM cell expansion and TNF-α-induced NF-κB signal. Moreover, 6-OAP exhibited potent anti-MM activity in nude mice and favorable pharmacokinetics in rats.Conclusions/SignificanceThese results indicate that 6-OAP is a new cell cycle inhibitor which shows therapeutic potentials for MM.

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