Transcription of the centromeric regions has been reported to occur in G1 and S phase in different species. Here, we investigate whether transcription also occurs and plays a functional role at the mammalian centromere during mitosis. We show the presence of actively transcribing RNA polymerase II (RNAPII) and its associated transcription factors, coupled with the production of centromere satellite transcripts at the mitotic kinetochore. Specific inhibition of RNAPII activity during mitosis leads to a decrease in centromeric α-satellite transcription and a concomitant increase in anaphase-lagging cells, with the lagging chromosomes showing reduced centromere protein C binding. These findings demonstrate an essential role of RNAPII in the transcription of α-satellite DNA, binding of centromere protein C, and the proper functioning of the mitotic kinetochore.
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http://dx.doi.org/10.1073/pnas.1108705109 | DOI Listing |
Biochemistry
January 2025
Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg 405 30, Sweden.
The apoptosome, a critical protein complex in apoptosis regulation, relies on intricate interactions between its components, particularly the proteins containing the Caspase Activation and Recruitment Domain (CARD). This work presents a thorough computational analysis of the stability and specificity of CARD-CARD interactions within the apoptosome. Departing from available crystal structures, we identify important residues for the interaction between the CARD domains of Apaf-1 and Caspase-9.
View Article and Find Full Text PDFArch Toxicol
January 2025
Department of Integrative Biology, School of Bioscience and Technology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India.
Snake envenomation presents a significant global health challenge, especially in rural areas of tropical and subtropical regions. Traditional antivenom therapies face limitations related to efficacy, availability, and specificity, prompting a need for novel approaches. Recent advancements in omics technologies, particularly metabolomics and proteomics, have enhanced our understanding of snake venom composition, toxicity, and potential therapeutic strategies.
View Article and Find Full Text PDFGraefes Arch Clin Exp Ophthalmol
January 2025
Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, No. 21 Jiefang Road, Xi'an, Shaanxi Province, 710004, China.
Purpose: Age-related cataract (ARC) remains one of the leading causes of blindness globally. Despite the satisfactory outcomes of surgical interventions, significant disparities in access to medical care prevent many patients from receiving effective treatment. Thus, identifying reliable biomarkers and therapeutic targets to expand treatment options for ARC is essential.
View Article and Find Full Text PDFJ Biochem
January 2025
Division of Cancer and Senescence Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
As the global population continues to age, understanding the complex role of cellular senescence and its implications in healthy lifespans has gained increasing prominence. Cellular senescence is defined as the irreversible cessation of cell proliferation, accompanied by the secretion of a range of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP), in response to various cellular stresses. While the accumulation of senescent cells has been strongly implicated in the aging process and the pathogenesis of age-related diseases owing to their pro-inflammatory properties, recent research has also highlighted their essential roles in processes such as tumour suppression, tissue development, and repair.
View Article and Find Full Text PDFMol Cell Biochem
January 2025
Neurodegenerative Diseases Laboratory, Center for Biomedicine, Universidad Mayor, Avenida Alemania 0281, 4780000, Temuco, La Araucanía, Chile.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by tremor, rigidity, and bradykinesia, beginning with early loss of dopaminergic neurons in the ventrolateral substantia nigra and advancing to broader neurodegeneration in the midbrain. The clinical heterogeneity of PD and the lack of specific diagnostic tests present significant challenges, highlighting the need for reliable biomarkers for early diagnosis. Alpha-synuclein (α-Syn), a protein aggregating into Lewy bodies and neurites in PD patients, has emerged as a key biomarker due to its central role in PD pathophysiology and potential to reflect pathological processes.
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