5-Aminouracil and other inhibitors of DNA replication induce biphasic interphase–mitotic cells in apical root meristems of Allium cepa

Abstract

Key message Induction of biphasic interphase-mitotic cells and PCC is connected with an increased level of metabolism in root meristem cells of Allium cepa.

Molecular Insights into How the Dimetal Center in Dihydropyrimidinase Can Bind the Thymine Antagonist 5‐Aminouracil: A Different Binding Mode from the Anticancer Drug 5‐Fluorouracil

“…5-AU also possesses potent anticancer activities that can block DNA synthesis and induce replication stress [ 11 ]. 5-AU can significantly induce biphasic interphase-mitotic (IM) cells [ 10 ]. Although 5-AU and 5-FU are similar uracil derivatives, no induction of IM cells was detected even using excess 5-FU [ 10 ].…”

“…5-AU can significantly induce biphasic interphase-mitotic (IM) cells [ 10 ]. Although 5-AU and 5-FU are similar uracil derivatives, no induction of IM cells was detected even using excess 5-FU [ 10 ]. Therefore, 5-AU and 5-FU might somehow induce different cellular effects.…”

“…For example, 5-fluorouracil (5-FU) is an FDA-approved drug with a remarkable therapeutic effect for the systemic treatment of cancers of the gastrointestinal tract, breast, head, and neck in the clinic [ 8 ]. As a thymine antagonist possessing anticancer activities, 5-aminouracil (5-AU) can block DNA synthesis and induce replication stress [ 10 , 11 ]. In addition, recent findings indicate that microbiota can modulate the host response to these chemotherapeutic drugs [ 12 ].…”

Epigenetic modifications evidenced by isolation of proteins on nascent DNA and immunofluorescence in hydroxyurea-treated root meristem cells of Vicia faba

“…Subsequently, samples were treated with 1 μl RNase A (20 mg/ml) for 30 min at 37 °C followed by Proteinase K (Sigma-Aldrich) treatment for 2 h at 45 °C (20 μl of 0.5 M EDTA, 40 μl of Tris pH 6.7 and 10 μl of Proteinase K). According to the procedure used earlier (Żabka et al 2020 ), samples containing 10 μl of DNA and 2 μl of gel loading buffer (0.25% bromophenol blue, 30% glycerol in 1 × TAE composed of 40 mM Tris–HCl, 1 mM EDTA, 40 mM acetic acid, pH 8.0) were applied to 1.5% agarose gel in 1 × TAE buffer with ethidium bromide (1 mg/ml) and separated by electrophoresis at 75 V for 3 h at RT. UV-fluorescent DNA fragments were photographed using a Gel UV Slider (Phoretix 1D image store system; Phoretix, England) in the Laboratory of Microscopic Imaging and Specialized Biological Techniques at the Faculty of Biology and Environmental Protection (University of Lodz).…”

Evaluation of Cytotoxic Effects of Methanolic Extract and Fractions of Mirabilis jalapa (L.) Leaf

“…The reduction in mitotic activity could also be due to inhibition of DNA synthesis which is one of the major prerequisites for cell division [24]. In biological system, there are some surveillance mechanisms that have been in place to detect different DNA damage which act in many ways to maintain genome integrity; one of the ways is the blockage of DNA replication to slow or stop cell cycle progression [25].…”