Chromosome instability is a major hallmark of cancer, but its molecular causes are still poorly understood. A study now describes how genetic alterations frequently found in colorectal cancer increase microtubule assembly rates during mitosis and promote chromosome instability.
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http://dx.doi.org/10.1038/ncb3018 | DOI Listing |
Nucleic Acids Res
January 2025
MOE Key Laboratory of Biosystems Homeostasis and Protection, College of Life Sciences, Zhejiang University, No.866 Yuhangtang Road, 310058, Hangzhou, China.
Meiosis in mammalian oocytes is interrupted by a prolonged arrest at the germinal vesicle stage, during which oocytes have to repair DNA lesions to ensure genome integrity or otherwise undergo apoptosis. The FIRRM/FLIP-FIGNL1 complex dissociates RAD51 from the joint DNA molecules in both homologous recombination (HR) and DNA replication. However, as a type of non-meiotic, non-replicative cells, whether this RAD51-dismantling mechanism regulates genome integrity in oocytes remains elusive.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Division of Hematology Oncology, Akron Children's Hospital, One Perkins Square, Akron, OH 44308, USA.
Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result in tissue fibrosis and genetic alterations that contribute to the pathogenesis of human diseases such as cancer. Recent scientific advancements exploring the underlying mechanisms of malignant cellular transformations and cancer progression have exposed significant disparities between pediatric and adult-onset cancers.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Centro de Investigación Biomédica en Red de Cáncer, CIBERONC CB16/12/00284, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Recent studies have demonstrated the association between constitutional ring chromosome 21 (r(21)c) and the development of B-cell acute lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21). iAMP21 acts as a driver which is often accompanied by secondary alterations that influence disease progression. Here, we report an atypical case of iAMP21 B-ALL with a unique molecular profile in the context of r(21)c.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
The presence of specific genetic mutations in patients with glioblastoma multiforme (GBM) is associated with improved survival outcomes. Disruption of the DNA damage response (DDR) pathway in tumor cells enhances the effectiveness of radiotherapy drugs, while increased mutational burden following tumor cell damage also facilitates the efficacy of immunotherapy. The ATRX gene, located on chromosome X, plays a crucial role in DDR.
View Article and Find Full Text PDFNat Cell Biol
January 2025
Department of Biochemistry, University of Oxford, Oxford, UK.
Delays in mitosis trigger p53-dependent arrest in G1 of the next cell cycle, thus preventing repeated cycles of chromosome instability and aneuploidy. Here we show that MDM2, the p53 ubiquitin ligase, is a key component of the timer mechanism triggering G1 arrest in response to prolonged mitosis. This timer function arises due to the attenuation of protein synthesis in mitosis.
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