Arabidopsis WEE1 kinase controls cell cycle arrest in response to activation of the DNA integrity checkpoint.
Upon the incidence of DNA stress, the ataxia telangiectasia-mutated (ATM) and Rad3-related (ATR) signaling kinases activate a transient cell cycle arrest that allows cells to repair DNA before proceeding into mitosis. Although the ATM-ATR pathway is highly conserved over species, the mechanisms by which plant cells stop their cell cycle in response to the loss of genome integrity are unclear. We demonstrate that the cell cycle regulatory WEE1 kinase gene of Arabidopsis thaliana is transcriptionally activated upon the cessation of DNA replication or DNA damage in an ATR- or ATM-dependent manner, respectively. In accordance with a role for WEE1 in DNA stress signaling, WEE1-deficient plants showed no obvious cell division or endoreduplication phenotype when grown under nonstress conditions but were hypersensitive to agents that impair DNA replication. Induced WEE1 expression inhibited plant growth by arresting dividing cells in the G2-phase of the cell cycle. We conclude that the plant WEE1 gene is not rate-limiting for cycle progression under normal growth conditions but is a critical target of the ATR-ATM signaling cascades that inhibit the cell cycle upon activation of the DNA integrity checkpoints, coupling mitosis to DNA repair in cells that suffer DNA damage.
De Schutter
Kristof
K
Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, B-9052 Gent, Belgium.
Joubès
Jérôme
J
Cools
Toon
T
Verkest
Aurine
A
Corellou
Florence
F
Babiychuk
Elena
E
Van Der Schueren
Els
E
Beeckman
Tom
T
Kushnir
Sergeï
S
Inzé
Dirk
D
De Veylder
Lieven
L
D016590:Aphidicolin / Q000494:pharmacology; D017360:Arabidopsis / Q000166:cytology* / Q000201:enzymology* / Q000254:growth & development; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D018506:Gene Expression Regulation, Plant; D006918:Hydroxyurea / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger; D036226:Seedlings / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction
C576589:ATM protein, Arabidopsis; D029681:Arabidopsis Proteins; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D016590:Aphidicolin; C576892:ATR protein, Arabidopsis; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C514674:WEE1 protein, Arabidopsis; C434472:CDKA1 protein, Arabidopsis; D018844:Cyclin-Dependent Kinases; D006918:Hydroxyurea