title: SB202190 affects cell response to hydroxyurea-induced genotoxic stress in root meristems of Vicia faba.
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.
authors.affiliation: Department of Cytophysiology, Faculty of Biology and Environmental Protection, University of Lodz, ul. Pomorska 141/143, 90-236 Lodz, Poland. winnicki@biol.uni.lodz.pl
authors.forename: Konrad
authors.initials: K
authors.lastname: Krajewski
authors.forename: Janusz
authors.initials: J
authors.lastname: Maszewski
mesh_terms: D000107:Acetylation / Q000187:drug effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000187:drug effects; D002110:Caffeine / Q000009:adverse effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D032461:Chromosomes, Plant / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D018744:DNA, Plant / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D006918:Hydroxyurea / Q000009:adverse effects; D007093:Imidazoles / Q000494:pharmacology*; D008239:Lysine / Q000378:metabolism; D018519:Meristem / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008938:Mitosis / Q000187:drug effects; D008940:Mitotic Index; D010940:Plant Proteins / Q000037:antagonists & inhibitors; D018517:Plant Roots / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D036226:Seedlings / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D031307:Vicia faba / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D018744:DNA, Plant; D004791:Enzyme Inhibitors; D006657:Histones; D007093:Imidazoles; D010940:Plant Proteins; D011725:Pyridines; D002110:Caffeine; D064007:Ataxia Telangiectasia Mutated Proteins; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D008239:Lysine; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D006918:Hydroxyurea