Appraisal of Cell Cycle Delay and Cytotoxicity Inducing Potential of 3-epicaryoptin in Allium Cepa L.

Diterpenoid 3-epicaryoptin (C26H36O9) is abundant in leaves of Clerodendrum inerme, a traditionally used medicinal plant, having insect antifeedant activities. Here, we aim to explore its cell cycle delay and cytotoxic effects in Allium cepa root apical meristem cells. Allium cepa roots were treated with 3-epicaryoptin and colchicine for 2, 4, 4+16 h (4 h treatment followed by 16 h recovery) and the induced cell cycle delay and cytotoxic effects were analyzed. The highest metaphase cells frequency for 3-epicaryoptin and colchicine treated samples were found to be 66.2% and 82.35% respectively at 4 h treatment. Treatment of 3-epicaryoptin and colchicine increased the aberrant cells %, CA, MN, c-metaphase, and PP cells. Therefore, indiscriminate use of C. inerme in traditional medicine should be restricted and the cell cycle delay and cytotoxicity inducing effects of 3-epicaryoptin needs further exploration for its cancer chemotherapeutic applications.

The conserved AAA-ATPase PCH-2 TRIP13 regulates spindle checkpoint strength

The length of the cell cycle delay imposed by the spindle checkpoint, also referred to as the spindle checkpoint strength, is controlled by the number of unattached kinetochores, cell volume, and cell fate. We show that PCH-2, a highly conserved AAA-ATPase, controls checkpoint strength during early embryogenesis in C. elegans.

Asymmetric Transcription Factor Partitioning During Yeast Cell Division Requires the FACT Chromatin Remodeler and Cell Cycle Progression

The polarized partitioning of proteins in cells underlies asymmetric cell division, which is an important driver of development and cellular diversity. The budding yeast Saccharomyces cerevisiae divides asymmetrically, like many other cells, to generate two distinct progeny cells. A well-known example of an asymmetric protein is the transcription factor Ace2, which localizes specifically to the daughter nucleus, where it drives a daughter-specific transcriptional network. We screened a collection of essential genes to analyze the effects of core cellular processes in asymmetric cell division based on Ace2 localization. This screen identified mutations that affect progression through the cell cycle, suggesting that cell cycle delay is sufficient to disrupt Ace2 asymmetry. To test this model, we blocked cells from progressing through mitosis and found that prolonged metaphase delay is sufficient to disrupt Ace2 asymmetry after release, and that Ace2 asymmetry is restored after cytokinesis. We also demonstrate that members of the evolutionarily conserved facilitates chromatin transcription (FACT) chromatin-reorganizing complex are required for both asymmetric and cell cycle-regulated localization of Ace2, and for localization of the RAM network components.

Rescue of DNA damage in cells after constricted migration reveals bimodal mechano-regulation of cell cycle

Migration through constrictions can clearly rupture nuclei and mis-localize nuclear proteins but damage to DNA remains uncertain as does any effect on cell cycle. Here, myosin-II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent delay in cell cycle is unaffected. Co-overexpression of multiple DNA repair factors and antioxidant inhibition of break formation also have partial effects, independent of rupture. Complete rescue of both DNA damage and cell cycle delay by myosin inhibition plus antioxidant reveals a bimodal dependence of cell cycle on DNA damage. Migration through custom-etched pores yields the same bimodal, with ~4-um pores causing intermediate levels of damage and cell cycle delay. Micronuclei (generated in faulty division) of the smallest diameter appear similar to ruptured nuclei, with high DNA damage and entry of chromatin-binding cGAS (cyclic-GMP-AMP-synthase) from cytoplasm but low repair factor levels. Increased genomic variation after constricted migration is quantified in expanding clones and is consistent with (mis)repair of excess DNA damage and subsequent proliferation.