0000000000431201

AUTHOR

Julia Damrot

showing 5 related works from this author

DNA replication arrest in response to genotoxic stress provokes early activation of stress-activated protein kinases (SAPK/JNK).

2009

Abstract The impact of DNA damage-induced replication blockage for early activation of stress kinases [stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)] is largely unknown. Here, we show that induction of dual phosphorylation of SAPK/JNK by the DNA polymerase inhibitor aphidicolin was not ameliorated by additional exposure to ultraviolet (UV) light, indicating that overlapping mechanisms participate in signaling to SAPK/JNK triggered by both agents. UV-induced DNA replication blockage, cyclobutane pyrimidine dimer formation and DNA strand break induction coincided with SAPK/JNK phosphorylation at early (≤ 30 min) but not late (≥ 2 h) time points after exposure. Genotoxin…

AphidicolinDNA ReplicationDNA damageUltraviolet RaysPoly ADP ribose polymeraseCell Linechemistry.chemical_compoundMiceAphidicolinStructural BiologyCricetinaeAnimalsHumansLymphocytesPhosphorylationProtein kinase AMolecular BiologyNucleic Acid Synthesis InhibitorsBRCA2 ProteinMice KnockoutbiologyKinaseCell CycleDNA replicationJNK Mitogen-Activated Protein KinasesFibroblastsMolecular biologyProliferating cell nuclear antigenDNA-Binding ProteinsEnzyme ActivationchemistryPyrimidine Dimersbiology.proteinPhosphorylationApoptosis Regulatory ProteinsDNA DamageJournal of molecular biology
researchProduct

Late Activation of Stress-activated Protein Kinases/c-Jun N-terminal Kinases Triggered by Cisplatin-induced DNA Damage in Repair-defective Cells

2011

Although stress-activated protein kinases/c-Jun N-terminal kinases (SAPK/JNK) are rapidly activated by genotoxins, the role of DNA damage in this response is not well defined. Here we show that the SEK1/MKK4-mediated dual phosphorylation of SAPK/JNK (Thr-183/Tyr-185) correlates with the level of cisplatin-DNA adducts at late times (16–24 h) after drug treatment in both human and mouse cells. Transfection of platinated plasmid DNA also caused SAPK/JNK activation. A defect in transcription-coupled nucleotide excision repair resting on a mutation in Cockayne syndrome group B protein promoted the late SAPK/JNK activation following cisplatin exposure. Signaling to SAPK/JNK was accompanied by act…

rho GTP-Binding ProteinsDNA RepairMAP Kinase Kinase 4DNA repairDNA damageDNA damage response; DNA repair; cisplatin-DNA adducts; SAPK/JNKp38 mitogen-activated protein kinasesAntineoplastic AgentsCell Cycle ProteinsAtaxia Telangiectasia Mutated ProteinsProtein Serine-Threonine KinasesDNA and ChromosomesBiologyBiochemistryAtaxia Telangiectasia Mutated ProteinsDNA AdductsMiceRadiation IonizingAnimalsHumansDNA Breaks Double-StrandedMolecular BiologyReplication protein ACells CulturedMice KnockoutKinaseTumor Suppressor ProteinsJNK Mitogen-Activated Protein KinasesCell BiologyMolecular biologyDNA-Binding ProteinsEnzyme Activationc-Jun N-terminal kinasesbiology.proteinCisplatinSignal TransductionNucleotide excision repairJournal of Biological Chemistry
researchProduct

Lovastatin protects human endothelial cells from the genotoxic and cytotoxic effects of the anticancer drugs doxorubicin and etoposide

2006

Background and purpose: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are frequently used lipid-lowering drugs. Moreover, they exert pleiotropic effects on cellular stress responses and death. Here, we analysed whether lovastatin affects the sensitivity of primary human endothelial cells (HUVEC) to the anticancer drug doxorubicin. Experimental approach: We investigated whether pretreatment of HUVEC with low dose of lovastatin influences the cellular sensitivity to doxorubicin. To this end, cell viability, proliferation and apoptosis as well as DNA damage-triggered stress response were analysed. Key results: Lovastatin reduced the cytotoxic potency of doxorub…

DNA ReplicationCell SurvivalDNA damageApoptosisBiologyPharmacologypolycyclic compoundsmedicineHumansTopoisomerase II InhibitorsDoxorubicinLovastatinEtoposideEtoposideFluorescent DyesPharmacologyAntibiotics AntineoplasticReverse Transcriptase Polymerase Chain ReactionTopoisomeraseCell CycleEndothelial Cellsnutritional and metabolic diseasesAntimutagenic AgentsFibroblastsCell cycleResearch PapersAntineoplastic Agents PhytogenicDoxorubicinDrug Resistance NeoplasmHMG-CoA reductasebiology.proteinlipids (amino acids peptides and proteins)LovastatinHydroxymethylglutaryl-CoA Reductase InhibitorsTopoisomerase-II InhibitorReactive Oxygen SpeciesFluorescein-5-isothiocyanateDNA Damagemedicine.drugBritish Journal of Pharmacology
researchProduct

Lovastatin protects human endothelial cells from killing by ionizing radiation without impairing induction and repair of DNA double-strand breaks.

2006

Abstract Purpose: 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (statins) are frequently used lipid-lowering drugs. Moreover, they are reported to exert pleiotropic effects on cellular stress responses, proliferation, and apoptosis. Whether statins affect the sensitivity of primary human cells to ionizing radiation (IR) is still unknown. The present study aims at answering this question. Experimental Design: The effect of lovastatin on IR-provoked cytotoxicity was analyzed in primary human umbilical vein endothelial cells (HUVEC). To this end, cell viability, proliferation, and apoptosis as well as DNA damage–related stress responses were investigated. Results: The data show that lova…

Cancer ResearchProgrammed cell deathDNA RepairDNA repairDNA damageCell SurvivalApoptosisRadioresistanceRadiation Ionizingpolycyclic compoundsmedicineHumansLovastatinCells CulturedCell Proliferationbiologynutritional and metabolic diseasesEndothelial CellsDose-Response Relationship RadiationDNAMolecular biologyEndothelial stem cellOncologyApoptosisCytoprotectionHMG-CoA reductasebiology.proteinCancer researchlipids (amino acids peptides and proteins)Lovastatinmedicine.drugDNA DamageClinical cancer research : an official journal of the American Association for Cancer Research
researchProduct

Cisplatin sensitivity is related to late DNA damage processing and checkpoint control rather than to the early DNA damage response

2008

The present study aimed at elucidating mechanisms dictating cell death triggered by cisplatin-induced DNA damage. We show that CL-V5B hamster mutant cells, a derivative of V79B, are hypersensitive to cisplatin-induced apoptotic death. CL-V5B cells are characterized by attenuated cisplatin-induced early (2-6 h) stress response, such as phosphorylation of stress-activated protein kinases (SAPK/JNK), ATM and Rad3-related (ATR) protein kinase, histone H2AX and checkpoint kinase-1 (Chk-1). Human FANCC cells also showed a reduced phosphorylation of H2AX and SAPK/JNK at early time point after cisplatin treatment. This was not the case for BRCA2-defective VC-8 hamster cells, indicating that the FA …

Cell cycle checkpointCisplatin-DNA adducts ; DNA repair ; Interstrand cross links ; DNA damage response ; Cell cycle checkpoint ; Cell deathDNA damageDNA repairHealth Toxicology and MutagenesisApoptosisCell LineHistonesDNA AdductsCricetinaeGeneticsmedicineAnimalsHumansCHEK1PhosphorylationMolecular BiologyChromosome AberrationsCisplatinbiologyJNK Mitogen-Activated Protein KinasesDNA replicationG2-M DNA damage checkpointMolecular biologyCell biologyHistonebiology.proteinCisplatinDNA DamageMutagensmedicine.drug
researchProduct