SB202190 affects cell response to hydroxyurea-induced genotoxic stress in root meristems of Vicia faba
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Published on: May 5, 2023
Konrad Krajewski1, Janusz Maszewski
1Department of Cytophysiology, Faculty of Biology and Environmental Protection, University of Lodz, ul. Pomorska 141/143, 90-236 Lodz, Poland. winnicki@biol.uni.lodz.pl
Abstract:
Genotoxic stress caused by a variety of chemical and physical agents may lead to DNA breaks and genome instability. Response to DNA damage depends on ATM/ATR sensor kinases and their downstream proteins, which arrange cell cycle checkpoints. Activation of ATM (ataxia-telangiectasia-mutated)/ATR (ATM and Rad 3-related) signaling pathway triggers cell cycle arrest (by keeping cyclin-Cdk complexes inactive), combined with gamma-phosphorylation of histone H2A.X and induction of DNA repair processes. However, genotoxic stress activates also mitogen-activated protein kinases (MAPKs) which may control the functions of checkpoint proteins both directly, by post-translational modifications, or indirectly, by regulation of their expression. Our results indicate that in root meristem cells of Vicia faba, MAP kinase signaling pathway takes part in response to hydroxyurea-induced genotoxic stress. It is shown that SB202190, an inhibitor of p38 MAP kinase, triggers PCC (premature chromosome condensation) more rapidly, but only if cell cycle checkpoints are alleviated by caffeine. Since SB202190 and, independently, caffeine reduces HU-mediated histone H4 Lys5 acetylation, it may be that there is a cooperation of MAP kinase signaling pathways and ATM/ATR-dependent checkpoints during response to genotoxic stress.
Insights
Mitogen-activated protein kinases (MAPKs) and ATM/ATR pathways cooperate in responding to genotoxic stress. This interaction influences cell cycle checkpoints and DNA repair in Vicia faba root meristem cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Genotoxic stress can cause DNA breaks and genome instability.
- ATM/ATR sensor kinases and their downstream proteins regulate cell cycle checkpoints in response to DNA damage.
- Mitogen-activated protein kinases (MAPKs) are also activated by genotoxic stress and can influence checkpoint protein function.
Purpose of the Study:
- To investigate the role of the MAP kinase signaling pathway in the response to hydroxyurea-induced genotoxic stress in Vicia faba root meristem cells.
- To explore the potential cooperation between MAP kinase signaling pathways and ATM/ATR-dependent checkpoints.
Main Methods:
- Utilized Vicia faba root meristem cells.
- Applied hydroxyurea (HU) to induce genotoxic stress.
- Used SB202190, a p38 MAP kinase inhibitor, and caffeine to modulate signaling pathways.
- Assessed premature chromosome condensation (PCC) and histone H4 Lys5 acetylation.
Main Results:
- MAP kinase signaling pathway participates in the response to hydroxyurea-induced genotoxic stress.
- SB202190 (p38 inhibitor) accelerated PCC when cell cycle checkpoints were alleviated by caffeine.
- Both SB202190 and caffeine reduced HU-mediated histone H4 Lys5 acetylation.
Conclusions:
- MAP kinase signaling pathways and ATM/ATR-dependent checkpoints likely cooperate in the cellular response to genotoxic stress.
- This cooperation may involve the regulation of histone modifications and cell cycle progression.
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