Review

Authors: Alejandra Vasquez-Limeta, Jadranka Loncarek

Centrosomes were first described by Edouard Van Beneden and named and linked to chromosome segregation by Theodor Boveri around 1870. In the 1960-1980s, electron microscopy studies have revealed the remarkable ultrastructure of a centriole -- a nine-fold symmetrical microtubular assembly that resides within a centrosome and organizes it. Less than two decades ago, proteomics and genomic screens conducted in multiple species identified hundreds of centriole and centrosome core proteins and revealed the evolutionarily conserved nature of the centriole assembly pathway. And now, super resolution microscopy approaches and improvements in cryo-tomography are bringing an unparalleled nanoscale-detailed picture of the centriole and centrosome architecture. In this chapter, we summarize the current knowledge about the architecture of human centrioles. We discuss the structured organization of centrosome components in interphase, focusing on localization/function relationship. We discuss the process of centrosome maturation and mitotic spindle pole assembly in centriolar and acentriolar cells, emphasizing recent literature.

Topics: Centrioles; Centrosome; Humans; Interphase

PubMed: 33836946
DOI: 10.1016/j.semcdb.2021.03.020

Authors: Robert Hasterok, Natalia Borowska-Zuchowska, Ewa Robaszkiewicz...

Modern molecular cytogenetics allows many aspects of the nuclear genome structure, function, and evolution to be analysed within the topographic context of mitotic and meiotic chromosomes and interphase nuclei [...].

Topics: Interphase; Cell Nucleus; Chromosomes; Cytogenetics; Genome

PubMed: 36361813
DOI: 10.3390/ijms232113028

Review

Authors: Isobel A MacGregor, Ian R Adams, Nick Gilbert...

The spatial configuration of chromatin is fundamental to ensure any given cell can fulfil its functional duties, from gene expression to specialised cellular division. Significant technological innovations have facilitated further insights into the structure, function and regulation of three-dimensional chromatin organisation. To date, the vast majority of investigations into chromatin organisation have been conducted in interphase and mitotic cells leaving meiotic chromatin relatively unexplored. In combination, cytological and genome-wide contact frequency analyses in mammalian germ cells have recently demonstrated that large-scale chromatin structures in meiotic prophase I are reminiscent of the sequential loop arrays found in mitotic cells, although interphase-like segmentation of transcriptionally active and inactive regions are also evident along the length of chromosomes. Here, we discuss the similarities and differences of such large-scale chromatin architecture, between interphase, mitotic and meiotic cells, as well as their functional relevance and the proposed modulatory mechanisms which underlie them.

Topics: Animals; Chromatin; Germ Cells; Humans; Interphase; Meiosis; Mitosis

PubMed: 31383821
DOI: 10.1042/BCJ20180512

Review

Authors: John M Ryniawec, Gregory C Rogers

The centrosome is a tiny cytoplasmic organelle that organizes and constructs massive molecular machines to coordinate diverse cellular processes. Due to its many roles during both interphase and mitosis, maintaining centrosome homeostasis is essential to normal health and development. Centrosome instability, divergence from normal centrosome number and structure, is a common pathognomonic cellular state tightly associated with cancers and other genetic diseases. As novel connections are investigated linking the centrosome to disease, it is critical to understand the breadth of centrosome functions to inspire discovery. In this review, we provide an introduction to normal centrosome function and highlight recent discoveries that link centrosome instability to specific disease states.

Topics: Animals; Centrosome; Chromosomal Instability; Genetic Diseases, Inborn; Humans; Interphase; Mitosis; Neoplasms; Organelles

PubMed: 34476544
DOI: 10.1007/s00018-021-03928-1

Review

Authors: R C Hankin, S V Hunter

OBJECTIVE

This article summarizes the most useful ancillary immunohistochemical and molecular assays for use in the diagnosis of mantle cell lymphoma.

DATA SOURCES

The English language literature was surveyed, with an emphasis on recent publications, for articles presenting key advances in the molecular characterization of mantle cell lymphomas and for series of cases testing the utility of molecular diagnostic tests. The authors' series of 26 small B-cell lymphomas, analyzed for the cyclin D1 protein by paraffin immunohistochemistry and for t(11;14) by polymerase chain reaction, is included.

CONCLUSIONS

Mantle cell lymphoma, a B-cell lymphoma now recognized in the 1994 Revised European-American Classification of Lymphoid Neoplasms (REAL) classification, is a relatively aggressive lymphoma with a poor prognosis. Its characteristic t(11;14)(q13;q32) translocation has a role in oncogenesis and has been exploited for molecular diagnostic tests, but these tests vary in sensitivity, specificity, and ease of use. Improved immunohistochemical tests are sufficient to confirm the diagnosis in most cases. Conventional cytogenetics and molecular diagnostic tests for t(11;14)-Southern blot and polymerase chain reaction analysis-may be helpful in selected cases, but are laborious or of limited sensitivity. Other methods, such as fluorescence in situ hybridization, need further development to provide faster, more sensitive diagnosis.

Topics: Cytogenetics; Humans; Immunophenotyping; Interphase; Lymphoma, B-Cell; Molecular Biology

PubMed: 10583923
DOI: 10.5858/1999-123-1182-MCL

Review

Authors: Jung Min Kim

Microtubules are major components of the cytoskeleton that play important roles in cellular processes such as intracellular transport and cell division. In recent years, it has become evident that microtubule networks play a role in genome maintenance during interphase. In this review, we highlight recent advances in understanding the role of microtubule dynamics in DNA damage response and repair. We first describe how DNA damage checkpoints regulate microtubule organization and stability. We then highlight how microtubule networks are involved in the nuclear remodeling following DNA damage, which leads to changes in chromosome organization. Lastly, we discuss how microtubule dynamics participate in the mobility of damaged DNA and promote consequent DNA repair. Together, the literature indicates the importance of microtubule dynamics in genome organization and stability during interphase.

Topics: Cell Nucleus; Centrosome; Cytoskeleton; DNA Damage; Interphase; Microtubules

PubMed: 35805981
DOI: 10.3390/ijms23136986

Review

Authors: Bernhard Lüscher, Maud Verheirstraeten, Sarah Krieg...

The innate immune system, the primary defense mechanism of higher organisms against pathogens including viruses, senses pathogen-associated molecular patterns (PAMPs). In response to PAMPs, interferons (IFNs) are produced, allowing the host to react swiftly to viral infection. In turn the expression of IFN-stimulated genes (ISGs) is induced. Their products disseminate the antiviral response. Among the ISGs conserved in many species are those encoding mono-ADP-ribosyltransferases (mono-ARTs). This prompts the question whether, and if so how, mono-ADP-ribosylation affects viral propagation. Emerging evidence demonstrates that some mono-ADP-ribosyltransferases function as PAMP receptors and modify both host and viral proteins relevant for viral replication. Support for mono-ADP-ribosylation in virus-host interaction stems from the findings that some viruses encode mono-ADP-ribosylhydrolases, which antagonize cellular mono-ARTs. We summarize and discuss the evidence linking mono-ADP-ribosylation and the enzymes relevant to catalyze this reversible modification with the innate immune response as part of the arms race between host and viruses.

Topics: ADP Ribose Transferases; Interphase; Pathogen-Associated Molecular Pattern Molecules; Virus Replication; Viruses

PubMed: 35536484
DOI: 10.1007/s00018-022-04290-6

Authors: Sarah He, Muhammed Sillah, Aidan R Cole...

BACKGROUND

Identifying cells engaged in fundamental cellular processes, such as proliferation or living/death statuses, is pivotal across numerous research fields. However, prevailing methods relying on molecular biomarkers are constrained by high costs, limited specificity, protracted sample preparation, and reliance on fluorescence imaging.

METHODS

Based on cellular morphology in phase contrast images, we developed a deep-learning model named Detector of Mitosis, Apoptosis, Interphase, Necrosis, and Senescence (D-MAINS).

RESULTS

D-MAINS utilizes machine learning and image processing techniques, enabling swift and label-free categorization of cell death, division, and senescence at a single-cell resolution. Impressively, D-MAINS achieved an accuracy of 96.4 ± 0.5% and was validated with established molecular biomarkers. D-MAINS underwent rigorous testing under varied conditions not initially present in the training dataset. It demonstrated proficiency across diverse scenarios, encompassing additional cell lines, drug treatments, and distinct microscopes with different objective lenses and magnifications, affirming the robustness and adaptability of D-MAINS across multiple experimental setups.

CONCLUSIONS

D-MAINS is an example showcasing the feasibility of a low-cost, rapid, and label-free methodology for distinguishing various cellular states. Its versatility makes it a promising tool applicable across a broad spectrum of biomedical research contexts, particularly in cell death and oncology studies.

Topics: Humans; Mitosis; Deep Learning; Apoptosis; Necrosis; Cellular Senescence; Interphase; Cell Line, Tumor; Neoplasms; Image Processing, Computer-Assisted

PubMed: 38920634
DOI: 10.3390/cells13121004

Review

Authors: Hisashi Miura, Ichiro Hiratani

In the mammalian cell nucleus, chromosomes are folded differently in interphase and mitosis. Interphase chromosomes are relatively decondensed and display at least two unique layers of higher-order organization: topologically associating domains (TADs) and cell-type-specific A/B compartments, which correlate well with early/late DNA replication timing (RT). In mitosis, these structures rapidly disappear but are gradually reconstructed during G1 phase, coincident with the establishment of the RT program. However, these structures also change dynamically during cell differentiation and reprogramming, and yet we are surprisingly ignorant about the relationship between their cell cycle dynamics and developmental dynamics. In this review, we summarize the recent findings on this topic, discuss how these two processes might be coordinated with each other and its potential significance.

Topics: Animals; Cell Cycle; Cell Nucleus; Chromatin; Chromosomes; Genome; Interphase; Mammals

PubMed: 35026526
DOI: 10.1016/j.gde.2021.101898

Authors: Tom van Schaik, Mabel Vos, Daan Peric-Hupkes...

In mammalian interphase nuclei, more than one thousand large genomic regions are positioned at the nuclear lamina (NL). These lamina-associated domains (LADs) are involved in gene regulation and may provide a backbone for the folding of interphase chromosomes. Little is known about the dynamics of LADs during interphase, in particular at the onset of G1 phase and during DNA replication. We developed an antibody-based variant of the DamID technology (named pA-DamID) that allows us to map and visualize genome-NL interactions with high temporal resolution. Application of pA-DamID combined with synchronization and cell sorting experiments reveals that LAD-NL contacts are generally rapidly established early in G1 phase. However, LADs on the distal ~25 Mb of most chromosomes tend to contact the NL first and then gradually detach, while centromere-proximal LADs accumulate gradually at the NL. Furthermore, our data indicate that S-phase chromatin shows transiently increased lamin interactions. These findings highlight a dynamic choreography of LAD-NL contacts during interphase progression and illustrate the usefulness of pA-DamID to study the dynamics of genome compartmentalization.

Topics: Animals; Cell Nucleus; Chromatin; Chromosomes; DNA; Interphase; Nuclear Lamina

PubMed: 32893442
DOI: 10.15252/embr.202050636