ArticleThe Journal of biological chemistry2011
TopBP1 deficiency causes an early embryonic lethality and induces cellular senescence in primary cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- TopBP1 orchestrates PU.1-IRF8 transcriptional programming of dendritic cell differentiation and Flt3L-driven tumor immunity.Experimental & molecular medicine · 2026Article
- ATR and TopBP1 oppose to control dormant origin activity and global replication dynamics, providing a first defense against replication stress.Nucleic acids research · 2026Article
- Defects in DNA damage signaling and cell cycle checkpoints in a mouse model of Rhno1 deletion.Cell death discovery · 2025Article
- Replication stress, microcephalic primordial dwarfism, and compromised immunity in ATRIP deficient patients.The Journal of experimental medicine · 2025Article
- Genome-wide association study applied to prolificacy in Santa Inês sheep.Tropical animal health and production · 2025Article
- Advances in the mechanism of small nucleolar RNA and its role in DNA damage response.Military Medical Research · 2024Review
- Phospholipase C-β3 is dispensable for vascular constriction but indispensable for vascular hyperplasia.Experimental & molecular medicine · 2024Article
- A TOPBP1 allele causing male infertility uncouples XY silencing dynamics from sex body formation.eLife · 2024Article
- Novel NF-κB reporter mouse for the non-invasive monitoring of inflammatory diseases.Scientific reports · 2023Article
- A function for ataxia telangiectasia and Rad3-related (ATR) kinase in cytokinetic abscission.iScience · 2022Article
- Mammalian eIF4E2-GSK3β maintains basal phosphorylation of p53 to resist senescence under hypoxia.Cell death & disease · 2022Article
- AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis.Nature communications · 2022Article
- DNA damage responses that enhance resilience to replication stress.Cellular and molecular life sciences : CMLS · 2021Review
- ATR regulates neuronal activity by modulating presynaptic firing.Nature communications · 2021Article
- NSMF promotes the replication stress-induced DNA damage response for genome maintenance.Nucleic acids research · 2021Article
- An Eye in the Replication Stress Response: Lessons From Tissue-Specific StudiesFrontiers in cell and developmental biology · 2021Review
- The neglected part of early embryonic development: maternal protein degradation.Cellular and molecular life sciences : CMLS · 2020Review
- Characterisation of unessential genes required for survival under conditions of DNA stress.Journal, genetic engineering & biotechnology · 2020Article
- A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis.Frontiers in cell and developmental biology · 2020Review
- Glycogen Synthase Kinase-3 Inhibition Sensitizes Pancreatic Cancer Cells to Chemotherapy by Abrogating the TopBP1/ATR-Mediated DNA Damage Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TopBP1 plays important roles in chromosome replication, DNA damage response, and other cellular regulatory functions in vertebrates. Although the roles of TopBP1 have been studied mostly in cancer cell lines, its physiological function remains unclear in mice and untransformed cells. We generated conditional knock-out mice in which exons 5 and 6 of the TopBP1 gene are flanked by loxP sequences. Although TopBP1-deficient embryos developed to the blastocyst stage, no homozygous mutant embryos were recovered at E8.5 or beyond, and completely resorbed embryos were frequent at E7.5, indicating that mutant embryos tend to die at the peri-implantation stage. This finding indicated that TopBP1 is essential for cell proliferation during early embryogenesis. Ablation of TopBP1 in TopBP1(flox/flox) mouse embryonic fibroblasts and 3T3 cells using Cre recombinase-expressing retrovirus arrests cell cycle progression at the G(1), S, and G(2)/M phases. The TopBP1-ablated mouse cells exhibit phosphorylation of H2AX and Chk2, indicating that the cells contain DNA breaks. The TopBP1-ablated mouse cells enter cellular senescence. Although RNA interference-mediated knockdown of TopBP1 induced cellular senescence in human primary cells, it induced apoptosis in cancer cells. Therefore, TopBP1 deficiency in untransformed mouse and human primary cells induces cellular senescence rather than apoptosis. These results indicate that TopBP1 is essential for cell proliferation and maintenance of chromosomal integrity.
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