Ploidy of thyroid parenchyma was studied in adult rats in the control and on day 9 after hemithyroidectomy; operated animals received 3 injections of N-nitroso-N-methylurea. The population of follicular thyrocytes is mainly diploid; total count of polyploid cells increased from 4.4% in the control to 8.5% in experimental rats. All thyrocytes containing micronuclei were tetraploid. No diploid micronucleated elements were detected. This suggests that genetically damaged thyrocytes divide by the mechanism of acytokinetic (polyploidizing) mitosis.
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Oxidative stress induces chromosomal instability through replication stress in fibroblasts from aged mice.
J Cell Sci
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Department of Molecular Oncology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Chromosomal aneuploidy has been associated with aging. However, whether and how chromosomal instability (CIN), a condition frequently seen in cancer cells in which chromosome missegregation occurs at a high rate, is associated with aging is not fully understood. Here, we found that primary fibroblasts isolated from aged mice (24 months old) exhibit an increased level of chromosome missegregation and micronucleation compared with that from young mice (2 months old), concomitant with an increased rate of aneuploid cells, suggesting the emergence of CIN.
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Cell
August 2022
Department of Obstetrics and Gynecology, Columbia University, New York, NY 10032, USA; Department of Pediatrics and Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA. Electronic address:
Human cleavage-stage embryos frequently acquire chromosomal aneuploidies during mitosis due to unknown mechanisms. Here, we show that S phase at the 1-cell stage shows replication fork stalling, low fork speed, and DNA synthesis extending into G2 phase. DNA damage foci consistent with collapsed replication forks, DSBs, and incomplete replication form in G2 in an ATR- and MRE11-dependent manner, followed by spontaneous chromosome breakage and segmental aneuploidies.
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Nature
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Oncode Institute, Hubrecht Institute-KNAW (Royal Academy of Arts and Sciences) and University Medical Centre Utrecht, Utrecht, the Netherlands.
Chromosome segregation errors during cell divisions generate aneuploidies and micronuclei, which can undergo extensive chromosomal rearrangements such as chromothripsis. Selective pressures then shape distinct aneuploidy and rearrangement patterns-for example, in cancer-but it is unknown whether initial biases in segregation errors and micronucleation exist for particular chromosomes. Using single-cell DNA sequencing after an error-prone mitosis in untransformed, diploid cell lines and organoids, we show that chromosomes have different segregation error frequencies that result in non-random aneuploidy landscapes.
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CNRS UMR9019 Genome Integrity and Cancers, Université Paris Saclay, Gustave Roussy, 94805 Villejuif, France.
Chromosomal instability (CIN) is associated with many human diseases, including neurodevelopmental or neurodegenerative conditions, age-related disorders and cancer, and is a key driver for disease initiation and progression. A major source of structural chromosome instability (s-CIN) leading to structural chromosome aberrations is "replication stress", a condition in which stalled or slowly progressing replication forks interfere with timely and error-free completion of the S phase. On the other hand, mitotic errors that result in chromosome mis-segregation are the cause of numerical chromosome instability (n-CIN) and aneuploidy.
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Probl Radiac Med Radiobiol
December 2019
Ivan Franko National University of Lviv, Faculty of Biology, 4 Mykhaila Hrushevskoho St., Lviv, 79005, Ukraine.
Objective: Rat liver stem-like epithelial cells (WB-F344) that under certain conditions may differentiate into hepa- tocyte and biliary lineages were subjected to acute X-irradiation with the aim to examine cell cycle peculiarities dur- ing the course of survival.
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