ArticleOncogene2013
Forced activation of Cdk1 via wee1 inhibition impairs homologous recombination.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 123 citations in OpenAlex.
- MUS81 inhibits cell proliferation and migration in breast cancer by promoting the expression of CDKN2A(p16American journal of translational research · 2026Article
- PLK1 or WEE1 inhibition targets homologous recombination repair proficiency in BRCA1/2 wild-type high-grade serous ovarian cancer.Cell death & disease · 2025Article
- Review
- 53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).Nature communications · 2024Article
- 53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).bioRxiv : the preprint server for biology · 2024Article
- ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors.British journal of cancer · 2024Article
- The Potential for Targeting GCancers · 2024Review
- G2 arrest primes hematopoietic stem cells for megakaryopoiesis.Cell reports · 2024Article
- Potential Benefits of Combining Proton or Carbon Ion Therapy with DNA Damage Repair Inhibitors.Cells · 2024Review
- An interphase actin wave promotes mitochondrial content mixing and organelle homeostasis.Nature communications · 2024Article
- Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage.Investigational new drugs · 2024Article
- P53 together with ferroptosis: a promising strategy leaving cancer cells without escape.Acta biochimica et biophysica Sinica · 2024Article
- Targeting WEE1 Kinase in Gynecological Malignancies.Drug design, development and therapy · 2024Review
- Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer.Frontiers in oncology · 2024Review
- Advances in molecular targeted therapies to increase efficacy of (chemo)radiation therapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- Review
- Article
- Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection.Computational and mathematical methods in medicine · 2023Article
- The life cycle of polyploid giant cancer cells and dormancy in cancer: Opportunities for novel therapeutic interventions.Seminars in cancer biology · 2022Review
- Pharmacologic Induction of BRCAness inCancers · 2022Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to DNA breaks, the 'DNA damage response' provokes a cell cycle arrest to facilitate DNA repair. Recent findings have indicated that cells can respond to DNA damage throughout the cell cycle, except during mitosis. Specifically, various mitotic kinases, including Cdk1, Aurora A and Plk1, were shown to inactivate key DNA damage checkpoint proteins when cells enter mitosis. Aberrant activation of mitotic kinases during interphase could therefore modulate cellular responses to DNA damage. In this study, our aim was to determine how aberrant activation of Cdk1 affects the cellular responses to DNA damage. We used Wee1 inhibition, using MK-1775, to force Cdk1 activation, which did not cause cytotoxicity in non-transformed cells. Instead, it accelerated mitotic entry and caused radio sensitization in p53-defective cancer cells, but not in p53-proficient cancer cells. Interestingly, we showed that Wee1 inhibition leads to elevation of Cdk1 activity in interphase cells. When we subsequently analyzed DNA damage responses in cells with forced Cdk1 activation, we observed a marked reduction of 53BP1 at sites of DNA damage along with an increase in γ-H2AX staining after irradiation, indicative of defective DNA repair. Indeed, when DNA repair was analyzed using in vivo endonuclease-induced homologous recombination (HR) assays, compromised DNA repair after Wee1 inhibition was confirmed. This defect in HR was accompanied by increased phosphorylation of BRCA2 at the Cdk1 phosphorylation site S3291. Taken together, our results indicate that Wee1 inhibition leads to forced Cdk1 activation in interphase cells, which interferes with normal DNA damage responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.