RRC ID 71930
Author Sunada S, Saito H, Zhang D, Xu Z, Miki Y.
Title CDK1 inhibitor controls G2/M phase transition and reverses DNA damage sensitivity.
Journal Biochem Biophys Res Commun
Abstract CDK1 plays key roles in cell cycle progression through the G2/M phase transition and activation of homologous recombination (HR) DNA repair pathway. Accordingly, various CDK1 inhibitors have been developed for cancer therapy that induce prolonged G2 arrest and/or sensitize cells to DNA damaging agents in tumor cells, resulting in cell death. However, CDK1 inhibition can induce resistance to DNA damage in certain conditions. The mechanism of different DNA damage sensitivity is not completely understood. We performed immunofluorescence and flow cytometry analysis to investigate DNA damage responses in human tumor cells during low and high dose treatments with RO-3306, a selective CDK1 inhibitor. This comparative investigation demonstrated that RO-3306-induced G2 arrest prevented cells with DNA double-strand breaks from transitioning into the M-phase and that the cells maintained their DNA repair capacity in G2-phase, even under RO-3306 dose-dependent DNA repair inhibition. These findings reveal that CDK1 inhibitor-induced DNA repair inhibition and cell cycle control, which regulate each other during the G2/M phase transition determine the cellular sensitivity to DNA damage, providing insight useful for developing clinical strategies targeting CDK1 inhibition in tumor cells.
Volume 550
Pages 56-61
Published 2021-4-23
DOI 10.1016/j.bbrc.2021.02.117
PII S0006-291X(21)00346-6
PMID 33684621
MeSH CDC2 Protein Kinase / antagonists & inhibitors* Cell Division / drug effects* Cell Line, Tumor DNA Damage / drug effects* G2 Phase Cell Cycle Checkpoints / drug effects* Humans Protein Kinase Inhibitors / pharmacology* Quinolines / pharmacology Recombinational DNA Repair / drug effects Thiazoles / pharmacology
IF 2.985
Human and Animal Cells HeLa