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High CDC20 levels increase sensitivity of cancer cells to MPS1 inhibitors.
EMBO Rep
January 2025
Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Spindle assembly checkpoint (SAC) inhibitors are a recently developed class of drugs, which perturb chromosome segregation during cell division, induce chromosomal instability (CIN), and eventually lead to cell death. The molecular features that determine cellular sensitivity to these drugs are not fully understood. We recently reported that aneuploid cancer cells are preferentially sensitive to SAC inhibition.
View Article and Find Full Text PDFTelomeres are hypersensitive to the formation of the common oxidative lesion 8-oxoguanine (8oxoG), which impacts telomere stability and function. OGG1 and MUTYH glycosylases initiate base excision repair (BER) to remove 8oxoG or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced premature senescence and associated proinflammatory responses, while loss of both glycosylases causes a near complete rescue in human fibroblasts.
View Article and Find Full Text PDFNKX6.3 modulation of mitotic dynamics and genomic stability in gastric carcinogenesis.
Cell Commun Signal
January 2025
Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, South Korea.
Background: Gastric cancer remains a significant global health challenge, characterized by poor prognosis and high mortality rates. Mitotic integrity and genomic stability are crucial in maintaining cellular homeostasis and preventing tumorigenesis. The transcription factor NKX6.
View Article and Find Full Text PDFCentromere positioning orchestrates telomere bouquet formation and the initiation of meiotic differentiation.
Nat Commun
January 2025
Instituto de Biología Funcional y Genómica, Zacarías González 2, Salamanca, 37007, Spain.
Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet.
View Article and Find Full Text PDFA dual role of Cohesin in DNA DSB repair.
Nat Commun
January 2025
Department of Hematopoietic Biology & Malignancy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cells undergo tens of thousands of DNA-damaging events each day. Defects in repairing double-stranded breaks (DSBs) can lead to genomic instability, contributing to cancer, genetic disorders, immunological diseases, and developmental defects. Cohesin, a multi-subunit protein complex, plays a crucial role in both chromosome organization and DNA repair by creating architectural loops through chromatin extrusion.
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