A5055784121- Cancer therapeutics and mechanisms
- Protein Degradation and Inhibitors
- ATP Synthase and ATPases Research
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Biochemical and Molecular Research
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Genetics, Aging, and Longevity in Model Organisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic factors in colorectal cancer
- RNA Research and Splicing
- Immune cells in cancer
- Mathematical Biology Tumor Growth
- FOXO transcription factor regulation
- Gene Regulatory Network Analysis
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- Cell death mechanisms and regulation
Utrecht University
2016-2025
Oncode Institute
2023-2025
University Medical Center Utrecht
2025
The Francis Crick Institute
2018-2022
Article2 September 2019Open Access Source DataTransparent process Cyclin F-dependent degradation of E2F7 is critical for DNA repair and G2-phase progression Ruixue Yuan orcid.org/0000-0001-9813-6683 Department Pathobiology, Faculty Veterinary Medicine, Utrecht University, Utrecht, The Netherlands Search more papers by this author Qingwu Liu Hendrika A Segeren orcid.org/0000-0002-8115-6482 Laurensia Yuniati Hubrecht Institute-KNAW University Medical Center Daniele Guardavaccaro Biotechnology,...
Oncogene‐induced replication stress (RS) is a vulnerability of cancer cells that forces reliance on the intra‐S‐phase checkpoint to ensure faithful genome duplication. Inhibitors kinases ATR and CHK1 have been developed, but resistance these drugs remains problematic. Understanding drug tolerance mechanisms impeded by analysis bulk samples, which neglect tumor heterogeneity often fail accurately interpret cell cycle‐mediated resistance. Here, combining intracellular immunostaining...
E2F transcription factors control the expression of cell-cycle genes. Cancers often demonstrate enhanced target gene expression, which can be explained by increased percentages replicating cells. However, we in human cancer biopsy specimens that individual neoplastic cells display abnormally high levels E2F-dependent transcription. To mimic this situation, delete atypical repressors (E2F7/8) or overexpress E2F3 activator untransformed Cells with elevated activity during S/G2 phase fail to...
The Topo2a-dependent arrest is associated with faithful segregation of sister chromatids and has been identified as dysfunctional in numerous tumour cell lines. This genome-protecting pathway poorly understood its characterization significant interest, potentially offering interventional opportunities relation to synthetic lethal behaviours arrest-defective tumours. Using the catalytic Topo2a inhibitor ICRF193, we have performed a genome-wide siRNA screen arrest-competent, non-transformed...
Abstract Cancer cells often experience high basal levels of DNA replication stress (RS), for example due to hyperactivation oncoproteins like MYC or RAS. Therefore, cancer are considered be sensitive drugs that exacerbate the level RS block intra S-phase checkpoint. Consequently, RS-inducing including ATR and CHK1 inhibitors used evaluated as anti-cancer therapies. However, drug resistance lack biomarkers predicting therapeutic efficacy limit efficient use. This raises question what...
Topoisomerase 2a (Topo2a)-dependent G2 arrest engenders faithful segregation of sister chromatids, yet in certain tumor cell lines where this is dysfunctional, a PKCε-dependent failsafe pathway can be triggered. Here we elaborate on recent advances understanding the underlying mechanisms associated with by determining that p53-p21 signaling essential for efficient lines, patient-derived cells, and colorectal cancer organoids. Regulation p53 axis required SMC5/6 complex, which distinct from...
Abstract Oncogene-induced replication stress (RS) is a vulnerability of cancer cells that forces reliance on the intra-S-phase checkpoint to ensure faithful genome duplication. Inhibitors crucial kinases ATR and CHK1 have been developed, but persistent proliferation resistance these drugs remain problematic. Understanding drug tolerance mechanisms impeded by analysis bulk samples, which neglect tumor heterogeneity often fail accurately interpret cell cycle-mediated resistance. Here,...
Abstract E2F transcription factors control the oscillating expression pattern of multiple target genes during cell cycle. Activator E2Fs, E2F1-3, induce an upswing targets, which is essential for G1-to-S phase transition, whereas atypical E2F7 and E2F8, mediate a downswing same targets late S, G2, M phase. Expression E2Fs induced by but it unknown how are inactivated in timely manner. Using molecular assays, time lapse microscopy, flow cytometry we now demonstrate that E2F8 substrates...
FACS sorting followed by single-cell RNA-sequencing (SORT-Seq) is a popular procedure to select cells of interest for transcriptomics. However, not suitable measurement subcellular distribution fluorescence or small samples (<1,000 cells). The VYCAP puncher system overcomes these limitations. Here, we describe workflow capture, image, and collect fluorescent human retina pigment epithelium SORT-Seq using this system. can be used any cell type with diameter ∼5-50 μm. For complete details on...
E2F transcription factors control the expression of a large network cell cycle genes and are essential for S-phase entry. Cancers often show upregulation target gene expression, which can be partially explained by an increased percentage replicating cells. However, we now demonstrate in human cancer biopsies that individual cycling neoplastic cells display abnormally high levels E2F-dependent using single RNA sequencing. Since patients treated with DNA damaging drugs, determined whether...
Abstract Cancer cells often experience high basal levels of DNA replication stress (RS), for example due to hyperactivation oncoproteins like MYC or RAS. Therefore, cancer are considered be sensitive drugs that exacerbate the level RS block intra S-phase checkpoint. Consequently, RS-inducing including ATR and CHK1 inhibitors used evaluated as anti-cancer therapies. However, drug resistance lack biomarkers predicting therapeutic efficacy limit efficient use. This raises question what...
<div>Abstract<p>Topoisomerase 2a (Topo2a)-dependent G<sub>2</sub> arrest engenders faithful segregation of sister chromatids, yet in certain tumor cell lines where this is dysfunctional, a PKCε-dependent failsafe pathway can be triggered. Here we elaborate on recent advances understanding the underlying mechanisms associated with by determining that p53–p21 signaling essential for efficient lines, patient-derived cells, and colorectal cancer organoids. Regulation p53...
Supplementary Figure from Genome-Protective Topoisomerase 2a-Dependent G<sub>2</sub> Arrest Requires p53 in hTERT-Positive Cancer Cells
<div>Abstract<p>Topoisomerase 2a (Topo2a)-dependent G<sub>2</sub> arrest engenders faithful segregation of sister chromatids, yet in certain tumor cell lines where this is dysfunctional, a PKCε-dependent failsafe pathway can be triggered. Here we elaborate on recent advances understanding the underlying mechanisms associated with by determining that p53–p21 signaling essential for efficient lines, patient-derived cells, and colorectal cancer organoids. Regulation p53...
Supplementary Figure from Genome-Protective Topoisomerase 2a-Dependent G<sub>2</sub> Arrest Requires p53 in hTERT-Positive Cancer Cells
Supplementary Figure from Genome-Protective Topoisomerase 2a-Dependent G<sub>2</sub> Arrest Requires p53 in hTERT-Positive Cancer Cells
Supplementary Figure from Genome-Protective Topoisomerase 2a-Dependent G<sub>2</sub> Arrest Requires p53 in hTERT-Positive Cancer Cells
Supplementary Figure from Genome-Protective Topoisomerase 2a-Dependent G<sub>2</sub> Arrest Requires p53 in hTERT-Positive Cancer Cells
Supplementary Figure from Genome-Protective Topoisomerase 2a-Dependent G<sub>2</sub> Arrest Requires p53 in hTERT-Positive Cancer Cells
Supplementary Figure from Genome-Protective Topoisomerase 2a-Dependent G<sub>2</sub> Arrest Requires p53 in hTERT-Positive Cancer Cells