Current Opinion in Cell Biology最新文献

Nuclear pore complexes (NPCs) are giant molecular assemblies that form the gateway between the nucleus and the cytoplasm and accommodate the bidirectional transport of a large variety of cargoes. Recent years have seen tremendous advances in our understanding of their building principles and have in particular called attention to the flexibility and variability of NPC composition and structure. Here, we review these recent advances and discuss how the newest technologies push the boundaries of nuclear pore research forward, with a specific highlight on the NPC scaffold and a prominent pore appendage, the nuclear basket, whose architecture has long been elusive.

Stable transmission of the genome during cell division is crucial for all life forms and is universally achieved by Aurora B-mediated error correction of the kinetochore-microtubule attachments. Aurora B is the enzymatic subunit of the tetrameric protein complex called the chromosomal passenger complex (CPC), and its centromeric enrichment is required for Aurora B to ensure accurate chromosome segregation. How cells enrich the CPC at centromeres is therefore an outstanding question to be elucidated. We review our recent understanding of how CPCs are assembled at inner centromeres in mitosis, the mechanism depending on mitotic histone phosphorylations and beyond.

Mitochondria are dynamic organelles essential for cellular homeostasis, undergoing continuous fission and fusion processes that regulate their morphology, distribution, and function. Disruptions in these dynamics are linked to numerous diseases, including neurodegenerative disorders and cancer. Understanding these processes is vital for developing therapeutic strategies aimed at mitigating mitochondrial dysfunction. This review provides an overview of recent perspectives on mitochondrial dynamics, focusing on the need for live video microscopy imaging in order to fully understand mitochondrial phenotypes and pathology. Advanced imaging tools, such as machine learning-based segmentation and label-free microscopy approaches, have the potential to transform our ability to study mitochondrial dynamics in live cells.

During mitosis, chromosomes condense, align to form a metaphase plate and segregate to the two daughter cells. Mitosis is one of the most complex recurring transformations in the life of a cell and requires a high degree of reliability to ensure the error-free transmission of genetic information to the next cell generation. An abnormally prolonged mitosis indicates potential defects that compromise genomic integrity. The mitotic stopwatch pathway detects even moderately prolonged mitoses by integrating memories of mitotic durations, ultimately leading to p53-mediated cell cycle arrest or death. This mechanism competes with mitogen signaling to stop the proliferation of damaged and potentially dangerous cells at a pre-oncogenic stage. Mitosis is a highly vulnerable phase, which is affected by multiple types of cellular damages and diverse stresses. We discuss the hypothesis that the duration of mitosis serves as an indicator of cell health.

Whilst DNA encodes our genetic blueprint as individual nucleobases, as well as epigenetic annotations in the form of biochemical marks, it also carries an extra layer of topological information -, the local over or underwinding of the double helix, known as DNA supercoiling. Supercoiling is a fundamental property of DNA that can be viewed as "topological epigenetics": it stores energy and structural information, and is tightly linked to fundamental processes; however, its quantification and study, by experiments and modelling alike, is challenging. We review experimental and simulation techniques to study supercoiling and its partition into twist and writhe, especially in the context of chromatin. We then discuss the dynamics of transcription-driven supercoiling in vitro and in vivo, and of supercoiling propagation along mammalian genomes. We finally provide evidence from the literature and potential mechanisms linking this ethereal topological mark to gene expression and chromosome instabilities in genetic diseases and cancer.