Temperature regulates negative supercoils to modulate meiotic crossovers and chromosome organization

Crossover recombination is a hallmark of meiosis that holds the paternal and maternal chromosomes(homologs)together for their faithful segregation,while promoting genetic diversity of the progeny.The pattern of crossover is mainly controlled by the architecture of the meiotic chromosomes.Environmental factors,especially temperature,also play an important role in modulating crossovers.However,it is unclear how temperature affects crossovers.Here,we examined the distribution of budding yeast axis components(Red1,Hop1,and Rec8)and the crossover-associated Zip3 foci in detail at different temperatures,and found that both increased and decreased temperatures result in shorter meiotic chromosome axes and more crossovers.Further investigations showed that temperature changes coordinately enhanced the hyperabundant accumulation of Hop1 and Red1 on chromosomes and the number of Zip3 foci.Most importantly,temperature-induced changes in the distribution of axis proteins and Zip3 foci depend on changes in DNA negative supercoils.These results suggest that yeast meiosis senses temperature changes by increasing the level of negative supercoils to increase crossovers and modulate chromosome organization.These findings provide a new perspective on understanding the effect and mechanism of temperature on meiotic recombination and chromosome organization,with important implications for evolution and breeding.

Galangin and TRAIL cooperate to suppress A549 lung cancer proliferation via apoptosis and p38 MAPK activation

Tumor necrosis factor-related apoptosis inducing ligand(TRAIL)is a promising antitumor therapy against lung cancer which is currently undergoing a phase II clinical trial in China.Unfortunately some cancer patients in the clinical trial displayed resistance to TR AIL treatment.In investigating ways to overcome this resistance,we evaluated the inhibitory effect of galangin on TRAIL resistant A549 human lung adenocarcinoma cells.Here we report that,in comparison with the single agents,the combination of galangin and TRAIL markedly suppressed proliferation of A549 cells and induced apoptosis as shown by DAPI and JC-1 staining.The combination of galangin and TRAIL induced PARP cleavage,activation of caspase-8 and p38 MAPK(mitogen-activated protein kinases).These findings indicate that the combination of galangin and TRAIL may constitute a promising strategy for the treatment of lung cancer.

Oridonin: A promising anticancer drug from China

Oridonin,a diterpenoid isolated from Rabdosia rubescens(Hemsl.)Hara,has been proved to possess remarkable anticancer activity,in addition to its potential in antiinflammation and antibacteria.The purpose of this article is to review current progress in oridonin concerned about a relationship between the chemical structure/modifications and its anticancer activity and to discuss the molecular mechanisms underlying its anticancer activity,such as suppression of tumor proliferation and induction of tumor cell death,and the cell signal transduction in anticancer activity of oridonin.