Pavlikova, M. | bioRxiv Science

bioRxiv2025

Condensin II mediates efficient chromatid resolution and resistance to genotoxic stress in Arabidopsis

Genome functions are regulated by the means of chromatin and 3D chromosome organization. Dynamic condensation and relaxation of chromosomes during cell cycle is largely controlled by the Condensin complexes. We mapped mutants in Condensin II subunits SMC2A, CAP-D3 and CAP-H2 as hypersensitive to DNA-protein crosslink (DPC) inducer zebularine. This suggested that Condensin II complex is required for resistance to genotoxic stress in Arabidopsis and prompted us to explore the underlying phenotypes. We show that the Condensin II role in resistance to zebularine is independent of the DNA damage response signaling by SOG1 and the homology-directed repair pathway. Furthermore, we found that Arabidopsis Condensin II mutants have incompletely condensed mitotic chromosomes and show abnormal chromatin connections during anaphase. Based on the structural and temporal analyses, we propose that the connections represent catenated chromatids. The chromosome connections were more frequent when the Condensin II mutants were treated by zebularine or TOP2 crosslinker and inhibitor ICRF-187. Altogether, we demonstrate that the proper large-scale chromatin organization by Condensin II is important for resistance to DNA damage response-inducing agents in Arabidopsis.

plant biology↗

bioRxiv2022

Cysteine Restriction-Specific Effects of Sulfur Amino Acid Restriction on Lipid Metabolism

Decreasing dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), i.e., sulfur amino acid restriction (SAAR). Contrarily, human diets used in clinical studies did not eliminate cysteine and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not with methionine, suggesting that CR, but not MR, is responsible for the antiadiposity effects of SAAR in rodents. Whether this is true, and if so, the underlying mechanisms are unknown. Using multiple diets with variable concentrations of methionine and cysteine, we demonstrate that the anti-adiposity effects of SAAR are due to CR. CR increased serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, essential for fatty acid/triglyceride cycling. Molecular data suggest that the CR results in glutathione depletion, which induces Nrf2 and downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. Using multiple mouse models, we show that the magnitude of SAAR-induced changes in molecular markers depends on dietary fat concentration (60 fat>10% fat), gender (males>females), and age-at-onset (young>adult). Our findings are translationally relevant as we found a negative correlation of plasma serine with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. SAAR-like diets with high polyunsaturated fatty acids increased plasma serine in a short-term human feeding study. Serinogenesis might be a potential target to correct hypertriglyceridemia.

biochemistry↗