S Phase Duration Is Determined by Local Rate and Global Organization of Replication

Greenberg, Alexander; Simon, Itamar

doi:10.3390/biology11050718

Cited by 11 publications

(7 citation statements)

References 132 publications

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“…1f , right panels), suggesting that there was an increase in origin firing frequency per each Q757X mutant cell undergoing DNA synthesis. Increasing origin firing can shorten S phase 24 , explaining the faster growth rate in the RECQ4 Q757X mutant cells. Shortening S phase is expected to decrease the S-phase population in asynchronized cells, but the ratio between G 1 - and S-phase populations did not change in asynchronized Q757X mutant cells compared to asynchronized WT cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation

Chang

et al. 2023

Nat Commun

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Deletion of the conserved C-terminus of the Rothmund-Thomson syndrome helicase RECQ4 is highly tumorigenic. However, while the RECQ4 N-terminus is known to facilitate DNA replication initiation, the function of its C-terminus remains unclear. Using an unbiased proteomic approach, we identify an interaction between the RECQ4 N-terminus and the anaphase-promoting complex/cyclosome (APC/C) on human chromatin. We further show that this interaction stabilizes APC/C co-activator CDH1 and enhances APC/C-dependent degradation of the replication inhibitor Geminin, allowing replication factors to accumulate on chromatin. In contrast, the function is blocked by the RECQ4 C-terminus, which binds to protein inhibitors of APC/C. A cancer-prone, C-terminal-deleted RECQ4 mutation increases origin firing frequency, accelerates G1/S transition, and supports abnormally high DNA content. Our study reveals a role of the human RECQ4 C-terminus in antagonizing its N-terminus, thereby suppressing replication initiation, and this suppression is impaired by oncogenic mutations.

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Section: Resultsmentioning

confidence: 99%

DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation

Chang

et al. 2023

Nat Commun

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“…protein that governs mitochondrial fission, may be crucial in maintaining tumorigenic cell proliferation in epithelial ovarian cancer (EOC) by mitosis boost [ 54 ]. The increased number of RAB-1 cells in the S-phase, simultaneously with the longer time needed for doubling time, can be related to the fact that cancer cell lines have longer S-phase than untransformed cells [ 55 – 57 ]. In turn, CHR-1 cells had lowered proliferative activity connected with increased cells in the G0/G1 phase of the cell cycle, which is also consistent with high mitochondrial membrane potential and tubular mitochondrial system characterizing that cells [ 58 ] but can also indicate their invasive potential [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of stromal-like cells with CD207+/low CD1a+/low phenotype derived from histiocytic lesions – a perspective in vitro model for drug testing

Śmieszek,

Marcinkowska,

Małas

et al. 2024

BMC Cancer

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Background Histiocytoses are rare disorders manifested by increased proliferation of pathogenic myeloid cells sharing histological features with macrophages or dendritic cells and accumulating in various organs, i.a., bone and skin. Pre-clinical in vitro models that could be used to determine molecular pathways of the disease are limited, hence research on histiocytoses is challenging. The current study compares cytophysiological features of progenitor, stromal-like cells derived from histiocytic lesions (sl-pHCs) of three pediatric patients with different histiocytoses types and outcomes. The characterized cells may find potential applications in drug testing. Methods Molecular phenotype of the cells, i.e. expression of CD1a and CD207 (langerin), was determined using flow cytometry. Cytogenetic analysis included GTG-banded metaphases and microarray (aCGH) evaluation. Furthermore, the morphology and ultrastructure of cells were evaluated using a confocal and scanning electron microscope. The microphotographs from the confocal imaging were used to reconstruct the mitochondrial network and its morphology. Basic cytophysiological parameters, such as viability, mitochondrial activity, and proliferation, were analyzed using multiple cellular assays, including Annexin V/7-AAD staining, mitopotential analysis, BrdU test, clonogenicity analysis, and distribution of cells within the cell cycle. Biomarkers potentially associated with histiocytoses progression were determined using RT-qPCR at mRNA, miRNA and lncRNA levels. Intracellular accumulation of histiocytosis-specific proteins was detected with Western blot. Cytotoxicyty and IC50 of vemurafenib and trametinib were determined with MTS assay. Results Obtained cellular models, i.e. RAB-1, HAN-1, and CHR-1, are heterogenic in terms of molecular phenotype and morphology. The cells express CD1a/CD207 markers characteristic for dendritic cells, but also show intracellular accumulation of markers characteristic for cells of mesenchymal origin, i.e. vimentin (VIM) and osteopontin (OPN). In subsequent cultures, cells remain viable and metabolically active, and the mitochondrial network is well developed, with some distinctive morphotypes noted in each cell line. Cell-specific transcriptome profile was noted, providing information on potential new biomarkers (non-coding RNAs) with diagnostic and prognostic features. The cells showed different sensitivity to vemurafenib and trametinib. Conclusion Obtained and characterized cellular models of stromal-like cells derived from histiocytic lesions can be used for studies on histiocytosis biology and drug testing.

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“…Rapidly multiplying cells of adult organisms, such as hematopoietic or basal cells of the epidermis and small intestine, may enter the cell cycle every 12–36 h. Short cell cycles (about 30 min) are observed in eggs of echinoderms, amphibians, and other animals. Under experimental conditions, many cell culture lines have cell cycles of about 20 h. The duration of the resting period between divisions in most actively dividing cells is about 10–24 h [ 46 , 47 , 48 , 49 ].…”

Section: Effect Of D/h Shift On Cell Proliferation and Apoptosismentioning

confidence: 99%

Emerging Role of Deuterium/Protium Disbalance in Cell Cycle and Apoptosis

Yaglova

Timokhina

Обернихин

et al. 2023

IJMS

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Deuterium, a stable isotope of hydrogen, is a component of water and organic compounds. It is the second most abundant element in the human body after sodium. Although the concentration of deuterium in an organism is much lower than that of protium, a wide variety of morphological, biochemical, and physiological changes are known to occur in deuterium-treated cells, including changes in fundamental processes such as cell division or energy metabolism. The mode and degree of changes in cells and tissues, both with an increase and a decrease in the concentration of deuterium, depends primarily on the time of exposure, as well as on the concentration. The reviewed data show that plant and animal cells are sensitive to deuterium content. Any shifts in the D/H balance outside or inside cells promote immediate responses. The review summarizes reported data on the proliferation and apoptosis of normal and neoplastic cells in different modes of deuteration and deuterium depletion in vivo and in vitro. The authors propose their own concept of the effects of changes in deuterium content in the body on cell proliferation and death. The altered rate of proliferation and apoptosis indicate a pivotal role of the hydrogen isotope content in living organisms and suggest the presence of a D/H sensor, which is yet to be detected.

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S Phase Duration Is Determined by Local Rate and Global Organization of Replication

Cited by 11 publications

References 132 publications

DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation

DNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation

Identification and characterization of stromal-like cells with CD207+/low CD1a+/low phenotype derived from histiocytic lesions – a perspective in vitro model for drug testing

Emerging Role of Deuterium/Protium Disbalance in Cell Cycle and Apoptosis

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