During meiosis, telomere attachment to the inner nuclear envelope is required for proper pairing of homologous chromosomes and recombination. Here, we identified F-box protein 47 (FBXO47) as a regulator of the telomeric shelterin complex that is specifically expressed during meiotic prophase I. Knockout of Fbxo47 in mice leads to infertility in males. We found that the Fbxo47 deficient spermatocytes are unable to form a complete synaptonemal complex. FBXO47 interacts with TRF1/2, and the disruption of Fbxo47 destabilizes TRF2, leading to unstable telomere attachment and slow traversing through the bouquet stage. Our findings uncover a novel mechanism of FBXO47 in telomeric shelterin subunit stabilization during meiosis.
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http://dx.doi.org/10.1093/nar/gkz992 | DOI Listing |
Nat Cell Biol
January 2025
CNRS UMR144 - UMR3664, Institut Curie, Sorbonne Université, PSL Research University, Paris, France.
Errors during cell division lead to aneuploidy, which is associated with genomic instability and cell transformation. In response to aneuploidy, cells activate the tumour suppressor p53 to elicit a surveillance mechanism that halts proliferation and promotes senescence. The molecular sensors that trigger this checkpoint are unclear.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Bone Pathophysiology Research Unit, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
Laminopathies represent a wide range of genetic disorders caused by mutations in gene-encoding proteins of the nuclear lamina. Altered nuclear mechanics have been associated with laminopathies, given the key role of nuclear lamins as mechanosensitive proteins involved in the mechanotransduction process. To shed light on the nuclear partners cooperating with altered lamins, we focused on Src tyrosine kinase, known to phosphorylate proteins of the nuclear lamina.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.
The nuclear envelope (NE), a protective membrane bordering the nucleus, is composed of highly specialized proteins that are indispensable for normal cellular activity. Lamina-associated polypeptide 1 (LAP1) is a NE protein whose functions are just beginning to be unveiled. The fact that mutations causing LAP1 deficiency are extremely rare and pathogenic is indicative of its paramount importance to preserving human health, anticipating that LAP1 might have a multifaceted role in the cell.
View Article and Find Full Text PDFCells
December 2024
State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China.
The nucleus serves as a pivotal regulatory and control hub in the cell, governing numerous aspects of cellular functions, including DNA replication, transcription, and RNA processing. Therefore, any deviations in nuclear morphology, structure, or organization can strongly affect cellular activities. In this review, we provide an updated perspective on the structure and function of nuclear components, focusing on the linker of nucleoskeleton and cytoskeleton complex, the nuclear envelope, the nuclear lamina, and chromatin.
View Article and Find Full Text PDFNat Nanotechnol
January 2025
ICFO-Institut de Ciències Fotòniques, Castelldefels, The Barcelona Institute of Science and Technology, Barcelona, Spain.
Quantifying the mechanical response of the biological milieu (such as the cell's interior) and complex fluids (such as biomolecular condensates) would enable a better understanding of cellular differentiation and aging and accelerate drug discovery. Here we present time-shared optical tweezer microrheology to determine the frequency- and age-dependent viscoelastic properties of biological materials. Our approach involves splitting a single laser beam into two near-instantaneous time-shared optical traps to carry out simultaneous force and displacement measurements and quantify the mechanical properties ranging from millipascals to kilopascals across five decades of frequency.
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