Article
Multidisciplinary Sciences
Simon Gemble, Rene Wardenaar, Kristina Keuper, Nishit Srivastava, Maddalena Nano, Anne-Sophie Mace, Andrea E. Tijhuis, Sara Vanessa Bernhard, Diana C. J. Spierings, Anthony Simon, Oumou Goundiam, Helfrid Hochegger, Matthieu Piel, Floris Foijer, Zuzana Storchova, Renata Basto
Summary: This study reveals that human cells experience high levels of DNA damage during DNA replication in the first S phase following tetraploidy induction. These damages are caused by protein shortage during the G1/S transition, resulting in inaccurate DNA replication. These findings provide an explanation for the genetic instability landscape that favors tumorigenesis after tetraploidization.
Review
Microbiology
Boris Bogdanow, Quang Vinh Phan, Luder Wiebusch
Summary: Cytomegaloviruses induce significant changes in cell cycle regulation to enable replication of their DNA genomes. They establish a unique cell cycle arrest at the G(1)/S transition, while activating S phase-specific gene expression and nucleotide metabolism. Despite similarities in cell cycle regulation between human and murine CMVs, there are considerable differences in viral cell cycle effectors and mechanisms of action.
Article
Multidisciplinary Sciences
Su-Lin Zeng, Suraj S. Patel, Mo-Qi Lv, Daphne Zhu, Wen H. Shen, Li Liu
Summary: In this study, the novel oncogene STYK1/NOK's role in cell division was investigated. It was found that STYK1/NOK interacts directly with CDH1 and can affect cell division by targeting key components of the APC/C pathway. These findings provide mechanistic clues for the understanding of STYK1/NOK's roles in mitosis and cytokinesis.
Review
Plant Sciences
Marina de Lyra Soriano Saleme, Ingrid Rocha Andrade, Nubia Barbosa Eloy
Summary: Most eukaryotic species propagate through sexual reproduction involving male and female gametes. In flowering plants, this process begins with DNA replication and chromosome segregation, followed by mitotic divisions to form male and female gametophytes. Precise regulation of gametogenesis progression is essential for successful meiotic cell division and sexual differentiation in plant species.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Cell Biology
Alex Willems, Lieven De Veylder
Summary: The review focuses on the plant APC/C complex, discussing its importance in plant development and its association with different developmental processes. The interactions between plant-specific APC/C activator subunits and other subunits are also described. Finally, a comprehensive list of confirmed and suspected plant APC/C target proteins is provided, offering opportunities to manipulate APC/C activity for increased crop yield and improved resilience to climate change.
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Eyashin Ali, Manash Jyoti Kalita, Simanta Kalita, Jayasree Talukdar, Ankur Jyoti Deka, Jasmin Sultana, Bikash Narayan Choudhury, Munindra Narayan Baruah, Sahana Bhattacharjee, Subhash Medhi
Summary: Esophageal squamous cell carcinoma (ESCC) is a prevalent type of esophageal cancer worldwide with a poor prognosis. Dysregulation of anaphase promoting complex/cyclosome (APC/C) activation due to altered expression of APC molecules may contribute to the development of ESCC. The study analyzed the expression of APC/C complex subunits and found significant upregulation of APC7 and APC3, which suggested their role in uncontrolled cell proliferation in ESCC. Additionally, lifestyle factors and their association with APC expression were also studied.
Article
Plant Sciences
Rodrigo Porto Schwedersky, Marina de Lyra Soriano Saleme, Ingrid Andrade Rocha, Patricia da Fonseca Montessoro, Adriana Silva Hemerly, Nubia Barbosa Eloy, Paulo Cavalcanti Gomes Ferreira
Summary: The study reveals the crucial role of APC11 in early plant development, mediating overall plant growth by regulating APC/C activity.
FRONTIERS IN PLANT SCIENCE
(2021)
Editorial Material
Biochemistry & Molecular Biology
Ilona Faustova, Mart Loog
Summary: Study by Hossain et al. (2021) reveals that ORC1 and CDC6 interact during pre-replicative complex formation in G1, mediated by SLiMs in IDRs and regulated by CDKs.
Review
Cell Biology
Tatyana Bodrug, Kaeli A. Welsh, Megan Hinkle, Michael J. Emanuele, Nicholas G. Brown
Summary: The ubiquitin-proteasome system plays a crucial role in cell cycle regulation, neurobiology, and chromatin control. Recent studies have revealed new mechanisms of APC/C activity and its involvement in broader signaling pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Genetics & Heredity
Yulong Li, Alexander J. Hartemink, David M. MacAlpine
Summary: This study investigated the dynamic changes in chromatin organization at and surrounding replication origins in Saccharomyces cerevisiae. It found that the downstream repositioning of the origin-proximal +1 nucleosome and an increase in protected DNA fragments spanning the ARS consensus sequence are indicative of pre-RC assembly. The strongest correlation between chromatin occupancy at the ACS and origin efficiency occurred in early S phase, consistent with the rate-limiting formation of the CMG complex being a determinant of origin activity. Nucleosome disruption and disorganization were observed emanating from replication origins and traveling with the elongating replication forks in S phase, reflecting the disassembly and assembly of chromatin ahead of and behind the replication fork.
Article
Biochemistry & Molecular Biology
Siyu Huang, Pin Wan, Shanyu Huang, Siyu Liu, Qi Xiang, Ge Yang, Muhammad Adnan Shereen, Pan Pan, Jun Wang, Weiyong Liu, Kailang Wu, Jianguo Wu
Summary: The study reveals that APC10 is a critical mediator in regulating NLRP3 inflammasome activation during the cell cycle, acting as a switch by interacting with NLRP3 to either promote or repress inflammatory responses.
Article
Microbiology
Kathrin Alpers, Elisabeth Vatareck, Lothar Groebe, Mathias Muesken, Maren Scharfe, Susanne Haeussler, Jurgen Tomasch
Summary: Pseudomonas aeruginosa undergoes a transition from fast growth with overlapping cell cycles to sustained slow growth with non-overlapping cell cycles when cultivated under standard laboratory conditions. This transition is characterized by sequential changes in transcriptional activity along the chromosome and a shift in quorum sensing activity. RNA sequencing of subpopulations identified distinct gene expression patterns for replicating and nonreplicating cells.
Review
Biochemistry & Molecular Biology
Jessica J. R. Hudson, Ulrich Rass
Summary: DNA2, a conserved nuclease-helicase, is crucial for cell proliferation and is implicated in DNA repair, checkpoint activation, and telomere homeostasis. Its critical role in replication stress response and recovery of stalled RFs makes it a promising target for anti-cancer therapy aimed at eliminating cancer cells by replication-stress overload.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Aneliya Ivanova, Aleksandar Atemin, Sonya Uzunova, Georgi Danovski, Radoslav Aleksandrov, Stoyno Stoynov, Marina Nedelcheva-Veleva
Summary: Cells have evolved mechanisms to regulate DNA replication and cell cycles in response to DNA damage and replication stress. The absence of Dia2 prolongs the cell cycle, increases cell size, and activates the S-phase checkpoint.
Article
Oncology
Mohaddase Hamidi, Ainhoa Eriz, Jone Mitxelena, Larraitz Fernandez-Ares, Igor Aurrekoetxea, Patricia Aspichueta, Ainhoa Iglesias-Ara, Ana M. Zubiaga
Summary: The study reveals that inhibiting E2F activity in prostate cancer cells can increase sensitivity to drug-induced replication stress and cell death. Furthermore, inhibiting E2F can also reduce the growth capacity of cancer cells when combined with drugs targeting nucleotide biosynthesis or DNA repair, suggesting a promising strategy for prostate cancer treatment.
Article
Gastroenterology & Hepatology
Martijn G. S. Rutten, Terry G. J. Derks, Nicolette C. A. Huijkman, Trijnie Bos, Niels J. Kloosterhuis, Kees C. W. A. van de Kolk, Justina C. Wolters, Mirjam H. Koster, Laura Bongiovanni, Rachel E. Thomas, Alain de Bruin, Bart van de Sluis, Maaike H. Oosterveer
Summary: This study developed a hepatocyte-specific GSD-1a mouse model using somatic CRISPR/Cas9-mediated gene editing, which successfully modeled a spectrum of GSD-1a phenotypes and allowed for the study of gene-gene interactions in the liver. This approach has potential for translational research and personalized treatments for GSD-1a and other genetic liver diseases.
Article
Veterinary Sciences
Laura Bongiovanni, Anneloes Andriessen, Serenella Silvestri, Ilaria Porcellato, Chiara Brachelente, Alain de Bruin
Summary: Uncontrolled proliferation is a key feature of tumor progression, with cell-cycle related factors potentially serving as cancer biomarkers. The Rb-E2F pathway could be targeted for effective anti-tumor therapy. CDK4/6 inhibitors show promise as a new anti-cancer treatment for canine melanoma, with H2AFZ potentially serving as a prognostic and predictive marker for patient selection.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
M. Guy Roukens, Cynthia L. Frederiks, Danielle Seinstra, Luca Braccioli, Antoine A. Khalil, Cornelieke Pals, Simon De Neck, Laura Bornes, Evelyne Beerling, Michal Mokry, Alain de Bruin, Bart Westendorp, Jacco van Rheenen, Paul J. Coffer
Summary: The transcription factor SOX4 plays a crucial role in the development of breast cancer, maintaining tumors in an undifferentiated and proliferative state by regulating stem cell genes. Knockout of SOX4 leads to differentiation of tumor cells, increase in luminal or basal gene expression, decrease in cell cycle gene expression, and impaired primary tumor growth and metastasis. Therapeutic manipulation of SOX4 function could be a promising strategy for cancer differentiation therapy.
Article
Veterinary Sciences
Anneloes Andriessen, Laura Bongiovanni, Tom A. P. Driedonks, Elsbeth van Liere, Anne Seijger, Charlotte Hegeman, Sebastiaan A. van Nimwegen, Sara Galac, Bart Westendorp, Esther N. M. Nolte-'t Hoen, Alain de Bruin
Summary: The study found that the levels of CDC6 mRNA were significantly higher in the plasma of canine tumor patients compared to healthy controls, and EV analysis enhanced the detectability of CDC6. This suggests that circulating CDC6 could be a promising non-invasive biomarker for diagnosing canine tumors.
VETERINARY AND COMPARATIVE ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Khashayar Roohollahi, Yvonne de Jong, Govind Pai, Mohamad Amr Zaini, Klaas de Lint, Daoud Sie, Martin A. Rooimans, Davy Rockx, Elizabeth E. Hoskins, Najim Ameziane, Rob Wolthuis, Hans Joenje, Susanne Wells, Josephine Dorsman
Summary: Head-and-neck squamous cell carcinomas (HNSCCs) are common in patients with Fanconi anemia (FA), and standard chemo-radiation therapy is not well tolerated in these patients. This study aimed to find alternative treatment options for FA-HNSCC by identifying genomic and transcriptomic events associated with the disease. The researchers used sequencing techniques to identify copy-number alterations in FA-HNSCC and found that amplification of 11q22.2 was a prevalent event. They also discovered that a small molecule inhibitor of BIRC2-3 could selectively kill FA tumor cells that overexpressed these genes. The findings suggest that inhibition of BIRC2-3 may be a potential therapeutic approach for FA-HNSCC.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Sara Carvalhal, Ingrid Bader, Martin A. Rooimans, Anneke B. Oostra, Jesper A. Balk, Rene G. Feichtinger, Christine Beichler, Michael R. Speicher, Johanna M. van Hagen, Quinten Waisfisz, Mieke van Haelst, Martijn Bruijn, Alexandra Tavares, Johannes A. Mayr, Rob M. F. Wolthuis, Raquel A. Oliveira, Job de Lange
Summary: BUB1 mutations cause neurodevelopmental disorder with cellular phenotypes similar to other syndromes.
Article
Chemistry, Multidisciplinary
Anders Marcher, Vipin Kumar, Veronica L. Andersen, Kassem El-Chami, Thuy J. D. Nguyen, Mads K. Skaanning, Imke Rudnik-Jansen, Jesper S. Nielsen, Kenneth A. Howard, Jorgen Kjems, Kurt V. Gothelf
Summary: Oligonucleotides are increasingly used as programmable connection materials for assembling molecules and proteins in well-defined structures. This study reports the application of aTNA, a type of oligonucleotide, in forming a highly stable four-way junction (4WJ) that allows easy assembly of components for in vivo treatment and imaging. The aTNA 4WJ is stable in serum, non-toxic, and does not induce an immune response.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Hendrika A. Segeren, Elsbeth A. van Liere, Frank M. Riemers, Alain de Bruin, Bart Westendorp
Summary: Cancer cells are often sensitive to drugs inducing DNA replication stress or blocking the intra S-phase checkpoint. However, drug resistance and lack of predictive biomarkers hinder their efficient use. The study reveals that transcriptional control of P53 target genes is the prime determinant in the response to ATR/CHK1 inhibitors, and hyperactivation of the MAPK pathway could impede this response.
Article
Gastroenterology & Hepatology
Eva Moreno, Augustine B. Matondo, Laura Bongiovanni, Chris H. A. van de Lest, Martijn R. Molenaar, Mathilda J. M. Toussaint, Saskia C. van Essen, Martin Houweling, J. Bernd Helms, Bart Westendorp, Alain de Bruin
Summary: The loss of tumor suppressor gene PTEN leads to hepatocellular polyploidization, lipid accumulation, and liver cancer development. Through the deletion of E2f7/8 genes, this study found that polyploidization promotes steatosis and acts as an important barrier against liver tumor progression.
LIVER INTERNATIONAL
(2022)
Article
Engineering, Biomedical
Elisabeth Fuchs, Imke Rudnik-Jansen, Anders Dinesen, Denis Selnihhin, Ole Aalund Mandrup, Kader Thiam, Jorgen Kjems, Finn Skou Pedersen, Kenneth A. Howard
Summary: The emergence of new SARS-CoV-2 mutants and breakthrough infections has led to the need for antiviral therapeutics. This study presents a recombinant human albumin ACE2 genetic fusion that can increase the plasma half-life and inhibit virus entry into cells. The fusion protein is shown to bind to the SARS-CoV-2 spike protein and inhibit viral infection.
ACTA BIOMATERIALIA
(2022)
Article
Oncology
Hendrika A. Segeren, Bart Westendorp
Summary: Activation of oncogenes in cancer cells leads to cell proliferation and DNA replication stress. Cancer cells heavily rely on the intra S-phase checkpoint for survival, making it a potential target for inhibitors such as ATR and CHK1. However, drug resistance hinders their clinical use. This review discusses the mechanisms by which cancer cells tolerate DNA replication stress, including increased nucleotide pool, enhanced stabilization and repair of stalled forks, and firing of dormant origins. It also proposes using E2F and NRF2 transcription factors as biomarkers and novel targets for killing RS-tolerant cancer cells.
Article
Immunology
Kathryn A. Wierenga, Frank M. Riemers, Bart Westendorp, Jack R. Harkema, James J. Pestka
Summary: This study used single-cell RNA sequencing to investigate the mechanism by which omega-3 polyunsaturated fatty acids (PUFAs) affect inflammatory response and interferon-regulated gene expression. The results showed that omega-3 PUFAs can alleviate inflammation and autoimmune diseases by modulating NF-kappa B and IFN1 responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Orthopedics
A. R. Tellegen, I. Rudnik-Jansen, L. Utomo, S. Versteeg, M. Beukers, R. Maarschalkerweerd, D. van Zuilen, N. J. van Klaveren, K. Houben, E. Teske, P. R. van Weeren, N. Karssemakers-Degen, G. Mihov, J. Thies, N. Eijkelkamp, L. B. Creemers, B. P. Meij, M. A. Tryfonidou
Summary: This study aimed to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB) for the treatment of osteoarthritis. The results showed that sustained release of CXB improved pain and quality of life in dogs with chronic osteoarthritis.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Microbiology
Maitrayee Chatterjee, Liane Z. X. L. Huang, Anna Mykytyn, Chunyan Wang, Mart B. Lamers, Bart Westendorp, Richard B. Wubbolts, Jos P. M. van Putten, Berend-Jan B. Bosch, Bart Haagmans, Karin B. Strijbis
Summary: In this study, the role of host mucins and mucin glycans on SARS-CoV-2 entry into airway epithelial cells was investigated. The removal of mucins from the surface of cells increased the binding of the virus and enhanced infection. This study demonstrates the important role of glycosylated extracellular mucin domains in the entry of SARS-CoV-2.
Article
Gastroenterology & Hepatology
Noortje Ijssennagger, Kristel S. van Rooijen, Stefania Magnusdottir, Jose M. Ramos Pittol, Ellen C. L. Willemsen, Marcel R. de Zoete, Matthijs J. D. Baars, Paul B. Stege, Carolina Colliva, Roberto Pellicciari, Sameh A. Youssef, Alain de Bruin, Yvonne Vercoulen, Folkert Kuipers, Saskia W. C. van Mil
Summary: This study highlights the importance of liver-to-gut communication for intestinal health, with a focus on colon functioning. Elimination of Fxr in the liver significantly affects colonic gene expression and enhances the protective capacity of the mucus barrier.
