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PLoS Genetics Sep 2019In all kingdoms of life, DNA is used to encode hereditary information. Propagation of the genetic material between generations requires timely and accurate duplication... (Review)
Review
In all kingdoms of life, DNA is used to encode hereditary information. Propagation of the genetic material between generations requires timely and accurate duplication of DNA by semiconservative replication prior to cell division to ensure each daughter cell receives the full complement of chromosomes. DNA synthesis of daughter strands starts at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, organisms have evolved surprisingly divergent strategies that control replication onset. Here, we discuss commonalities and differences in replication origin organization and recognition in the three domains of life.
Topics: Biological Evolution; Cell Division; Chromosomes; DNA Replication; Evolution, Molecular; Replication Origin; Replicon
PubMed: 31513569
DOI: 10.1371/journal.pgen.1008320 -
Aging Cell Apr 2021The field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal... (Review)
Review
The field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal and clinical research. Cellular senescence is defined by a set of markers, many of which are present and accumulate in a gradual manner prior to senescence induction or are found outside of the context of cellular senescence. These markers are now used to measure the impact of cellular senescence on aging and disease as well as outcomes of anti-senescence interventions, many of which are at the stage of clinical trials. It is thus of primary importance to discuss their specificity as well as their role in the establishment of senescence. Here, the presence and role of senescence markers are described in cells prior to cell cycle arrest, especially in the context of replicative aging and in vivo conditions. Specifically, this review article seeks to describe the process of "cellular aging": the progression of internal changes occurring in primary cells leading to the induction of cellular senescence and culminating in cell death. Phenotypic changes associated with aging prior to senescence induction will be characterized, as well as their effect on the induction of cell senescence and the final fate of cells reviewed. Using published datasets on assessments of senescence markers in vivo, it will be described how disparities between quantifications can be explained by the concept of cellular aging. Finally, throughout the article the applicational value of broadening cellular senescence paradigm will be discussed.
Topics: Aging; Animals; Biomarkers; Cell Cycle Checkpoints; Cell Division; Cell Proliferation; Cell Size; Cellular Senescence; DNA Breaks, Double-Stranded; Humans; Phenotype; Telomere Shortening
PubMed: 33711211
DOI: 10.1111/acel.13338 -
Nature Immunology Sep 2023Tumor-specific CD8+ T cells (TST) in patients with cancer are dysfunctional and unable to halt cancer progression. TST dysfunction, also known as exhaustion, is thought...
Tumor-specific CD8+ T cells (TST) in patients with cancer are dysfunctional and unable to halt cancer progression. TST dysfunction, also known as exhaustion, is thought to be driven by chronic T cell antigen receptor (TCR) stimulation over days to weeks. However, we know little about the interplay between CD8 T cell function, cell division and epigenetic remodeling within hours of activation. Here, we assessed early CD8 T cell differentiation, cell division, chromatin accessibility and transcription in tumor-bearing mice and acutely infected mice. Surprisingly, despite robust activation and proliferation, TST had near complete effector function impairment even before undergoing cell division and had acquired hallmark chromatin accessibility features previously associated with later dysfunction/exhaustion. Moreover, continued tumor/antigen exposure drove progressive epigenetic remodeling, 'imprinting' the dysfunctional state. Our study reveals the rapid divergence of T cell fate choice before cell division in the context of tumors versus infection.
Topics: Mice; Animals; CD8-Positive T-Lymphocytes; Neoplasms; Cell Division; Antigens, Neoplasm; Chromatin; Receptors, Antigen, T-Cell
PubMed: 37537361
DOI: 10.1038/s41590-023-01578-y -
Molecules (Basel, Switzerland) Jul 2022Cancer is a multifactorial disorder caused by several aberrations in gene expression that generate a homeostatic imbalance between cell division and death [...].
Cancer is a multifactorial disorder caused by several aberrations in gene expression that generate a homeostatic imbalance between cell division and death [...].
Topics: Cell Division; Humans; Neoplasms
PubMed: 35889522
DOI: 10.3390/molecules27144650 -
EcoSal Plus Jan 2021Peptidoglycan is a defining feature of the bacterial cell wall. Initially identified as a target of the revolutionary beta-lactam antibiotics, peptidoglycan has become a...
Peptidoglycan is a defining feature of the bacterial cell wall. Initially identified as a target of the revolutionary beta-lactam antibiotics, peptidoglycan has become a subject of much interest for its biology, its potential for the discovery of novel antibiotic targets, and its role in infection. Peptidoglycan is a large polymer that forms a mesh-like scaffold around the bacterial cytoplasmic membrane. Peptidoglycan synthesis is vital at several stages of the bacterial cell cycle: for expansion of the scaffold during cell elongation and for formation of a septum during cell division. It is a complex multifactorial process that includes formation of monomeric precursors in the cytoplasm, their transport to the periplasm, and polymerization to form a functional peptidoglycan sacculus. These processes require spatio-temporal regulation for successful assembly of a robust sacculus to protect the cell from turgor and determine cell shape. A century of research has uncovered the fundamentals of peptidoglycan biology, and recent studies employing advanced technologies have shed new light on the molecular interactions that govern peptidoglycan synthesis. Here, we describe the peptidoglycan structure, synthesis, and regulation in rod-shaped bacteria, particularly , with a few examples from and other diverse organisms. We focus on the pathway of peptidoglycan sacculus elongation, with special emphasis on discoveries of the past decade that have shaped our understanding of peptidoglycan biology.
Topics: Cell Division; Cell Membrane; Cell Wall; Escherichia coli; Peptidoglycan
PubMed: 33470191
DOI: 10.1128/ecosalplus.ESP-0010-2020 -
Science (New York, N.Y.) Jul 2020Cell size is fundamental to cell physiology. For example, cell size determines the spatial scale of organelles and intracellular transport and thereby affects...
Cell size is fundamental to cell physiology. For example, cell size determines the spatial scale of organelles and intracellular transport and thereby affects biosynthesis. Although some genes that affect mammalian cell size have been identified, the molecular mechanisms through which cell growth drives cell division have remained elusive. We show that cell growth during the G phase of the cell division cycle dilutes the cell cycle inhibitor Retinoblastoma protein (Rb) to trigger division in human cells. overexpression increased cell size and G duration, whereas deletion decreased cell size and removed the inverse correlation between cell size at birth and the duration of the G phase. Thus, Rb dilution through cell growth in G provides one of the long-sought molecular mechanisms that promotes cell size homeostasis.
Topics: Cell Cycle Checkpoints; Cell Division; Cell Proliferation; Cell Size; G1 Phase; Humans; Retinoblastoma Protein
PubMed: 32703881
DOI: 10.1126/science.aaz6213 -
Development (Cambridge, England) Feb 2021Quiescence is a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide. The unique ability of adult stem cells to maintain... (Review)
Review
Quiescence is a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide. The unique ability of adult stem cells to maintain quiescence is crucial for life-long tissue homeostasis and regenerative capacity. Quiescence has long been viewed as an inactive state but recent studies have shown that it is in fact an actively regulated process and that adult stem cells are highly reactive to extrinsic stimuli. This has fuelled hopes of boosting the reactivation potential of adult stem cells to improve tissue function during ageing. In this Review, we provide a perspective of the quiescent state and discuss how quiescent adult stem cells transition into the cell cycle. We also discuss current challenges in the field, highlighting recent technical advances that could help overcome some of these challenges.
Topics: Adult Stem Cells; Cell Cycle; Cell Differentiation; Cell Division; Cell Proliferation; Epigenomics; Homeostasis; Humans; Stem Cells
PubMed: 33558315
DOI: 10.1242/dev.165084 -
Cells Feb 2022All living organisms on Earth are made up of cells, which are the functional unit of life. Eukaryotic organisms can consist of a single cell (unicellular) or a group of... (Review)
Review
All living organisms on Earth are made up of cells, which are the functional unit of life. Eukaryotic organisms can consist of a single cell (unicellular) or a group of either identical or different cells (multicellular). Biologists have always been fascinated by how a single cell, such as an egg, can give rise to an entire organism, such as the human body, composed of billions of cells, including hundreds of different cell types. This is made possible by cell division, whereby a single cell divides to form two cells. During a symmetric cell division, a mother cell produces two daughter cells, while an asymmetric cell division results in a mother and a daughter cell that have different fates (different morphologies, cellular compositions, replicative potentials, and/or capacities to differentiate). In biology, the cell cycle refers to the sequence of events that a cell must go through in order to divide. These events, which always occur in the same order, define the different stages of the cell cycle: G1, S, G2, and M. What is fascinating about the cell cycle is its universality, and the main reason for this is that the genetic information of the cell is encoded by exactly the same molecular entity with exactly the same structure: the DNA double helix. Since both daughter cells always inherit their genetic information from their parent cell, the underlying fundamentals of the cell cycle-DNA replication and chromosome segregation-are shared by all organisms. This review goes back in time to provide a historical summary of the main discoveries that led to the current understanding of how cells divide and how cell division is regulated to remain highly reproducible.
Topics: Cell Cycle; Cell Cycle Checkpoints; Cell Division; DNA Replication; Humans
PubMed: 35203358
DOI: 10.3390/cells11040704 -
International Journal of Molecular... Mar 2022Human female fertility and reproductive lifespan decrease significantly with age, resulting in an extended post-reproductive period. The central dogma in human female... (Review)
Review
Human female fertility and reproductive lifespan decrease significantly with age, resulting in an extended post-reproductive period. The central dogma in human female reproduction contains two important aspects. One is the pool of oocytes in the human ovary (the ovarian reserve; approximately 10 at birth), which diminishes throughout life until menopause around the age of 50 (approximately 10 oocytes) in women. The second is the quality of oocytes, including the correctness of meiotic divisions, among other factors. Notably, the increased rate of sub- and infertility, aneuploidy, miscarriages, and birth defects are associated with advanced maternal age, especially in women above 35 years of age. This postponement is also relevant for human evolution; decades ago, the female aging-related fertility drop was not as important as it is today because women were having their children at a younger age. Spindle assembly is crucial for chromosome segregation during each cell division and oocyte maturation, making it an important event for euploidy. Consequently, aberrations in this segregation process, especially during the first meiotic division in human eggs, can lead to implantation failure or spontaneous abortion. Today, human reproductive medicine is also facing a high prevalence of aneuploidy, even in young females. However, the shift in the reproductive phase of humans and the strong increase in errors make the problem much more dramatic at later stages of the female reproductive phase. Aneuploidy in human eggs could be the result of the non-disjunction of entire chromosomes or sister chromatids during oocyte meiosis, but partial or segmental aneuploidies are also relevant. In this review, we intend to describe the relevance of the spindle apparatus during oocyte maturation for proper chromosome segregation in the context of maternal aging and the female reproductive lifespan.
Topics: Aging; Aneuploidy; Chromosome Segregation; Female; Humans; Meiosis; Oocytes; Pregnancy; Spindle Apparatus
PubMed: 35270022
DOI: 10.3390/ijms23052880 -
Journal of Cell Science Sep 2020Human retinal pigment epithelial-1 (RPE-1) cells are increasingly being used as a model to study mitosis because they represent a non-transformed alternative to cancer...
Human retinal pigment epithelial-1 (RPE-1) cells are increasingly being used as a model to study mitosis because they represent a non-transformed alternative to cancer cell lines, such as HeLa cervical adenocarcinoma cells. However, the lack of an efficient method to synchronize RPE-1 cells in mitosis precludes their application for large-scale biochemical and proteomics assays. Here, we report a protocol to synchronize RPE-1 cells based on sequential treatments with the Cdk4 and Cdk6 inhibitor PD 0332991 (palbociclib) and the microtubule-depolymerizing drug nocodazole. With this method, the vast majority (80-90%) of RPE-1 cells arrested at prometaphase and exited mitosis synchronously after release from nocodazole. Moreover, the cells fully recovered and re-entered the cell cycle after the palbociclib-nocodazole block. Finally, we show that this protocol could be successfully employed for the characterization of the protein-protein interaction network of the kinetochore protein Ndc80 by immunoprecipitation coupled with mass spectrometry. This synchronization method significantly expands the versatility and applicability of RPE-1 cells to the study of cell division and might be applied to other cell lines that do not respond to treatments with DNA synthesis inhibitors.
Topics: Humans; Kinetochores; Mitosis; Nocodazole; Prometaphase; Retinal Pigments
PubMed: 32878943
DOI: 10.1242/jcs.247940