WEE1 inhibition enhances sensitivity to hypoxia/reoxygenation in HeLa cells.
BRCA1 Protein
/ metabolism
Cell Cycle Proteins
/ antagonists & inhibitors
Cell Hypoxia
/ drug effects
Cell Survival
/ drug effects
Clone Cells
G2 Phase Cell Cycle Checkpoints
/ drug effects
HeLa Cells
Humans
Kinetics
Mitosis
/ drug effects
Oxygen
/ pharmacology
Protein-Tyrosine Kinases
/ antagonists & inhibitors
Pyrazoles
/ pharmacology
Pyrimidinones
/ pharmacology
DNA double-strand breaks
WEE1
homologous recombination
hypoxia
reoxygenation
Journal
Journal of radiation research
ISSN: 1349-9157
Titre abrégé: J Radiat Res
Pays: England
ID NLM: 0376611
Informations de publication
Date de publication:
23 10 2019
23 10 2019
Historique:
received:
01
02
2019
revised:
16
05
2019
pubmed:
28
7
2019
medline:
7
3
2020
entrez:
27
7
2019
Statut:
ppublish
Résumé
Hypoxia/reoxygenation (H/R) treatment reportedly induces DNA damage response (DDR), including DNA double-strand break (DSB) repair and G2 arrest, resulting in reduction of clonogenic survival. Because WEE1 plays a key role in the G2/M checkpoint along with CHK1/2, we investigated the effect of WEE1 inhibition on H/R-induced DDR using HeLa cells. The H/R treatment combined with WEE1 inhibitor abrogated G2 arrest, subsequently leading to the cells entering the M phase, and finally resulting in mitotic catastrophe after prolonged mitosis. Colony-forming assay showed an enhanced decrease in the surviving fraction and the focus formation of BRCA1 was significantly reduced. We demonstrate for the first time that WEE1 inhibition enhances H/R-induced cell death accompanied by mitotic catastrophe and that the process may be mediated by homologous recombination.
Identifiants
pubmed: 31347653
pii: 5539284
doi: 10.1093/jrr/rrz045
pmc: PMC6805980
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
Cell Cycle Proteins
0
Pyrazoles
0
Pyrimidinones
0
Protein-Tyrosine Kinases
EC 2.7.10.1
WEE1 protein, human
EC 2.7.10.2
adavosertib
K2T6HJX3I3
Oxygen
S88TT14065
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
709-713Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.
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