Search results for "Dama"
showing 10 items of 1437 documents
FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability
2021
Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and pr…
Dicer prevents genome instability in response to replication stress
2019
Dicer, an endoribonuclease best-known for its role in microRNA biogenesis and RNA interference pathway, has been shown to play a role in the DNA damage response and repair of double-stranded DNA breaks (DSBs) in mammalian cells. However, it remains unknown whether Dicer is also important to preserve genome integrity upon replication stress. To address this question, we focused our study on common fragile sites (CFSs), which are susceptible to breakage after replication stress. We show that inhibition of the Dicer pathway leads to an increase in CFS expression upon induction of replication stress and to an accumulation of 53BP1 nuclear bodies, indicating transmission of replication-associate…
Role of the DNA repair glycosylase OGG1 in the activation of murine splenocytes
2017
OGG1 (8-oxoguanine-DNA glycosylase) is the major DNA repair glycosylase removing the premutagenic DNA base modification 8-oxo-7,8-dihydroguanine (8-oxoG) from the genome of mammalian cells. In addition, there is accumulating evidence that OGG1 and its substrate 8-oxoG might function in the regulation of certain genes, which could account for an attenuated immune response observed in Ogg1-/- mice in several settings. Indications for at least two different mechanisms have been obtained. Thus, OGG1 could either act as an ancillary transcription factor cooperating with the lysine-specific demethylase LSD1 or as an activator of small GTPases. Here, we analysed the activation by lipopolysaccaride…
Free energy profiles for two ubiquitous damaging agents: methylation and hydroxylation of guanine in B-DNA
2017
International audience; DNA methylation and hydroxylation are two ubiquitous reactions in DNA damage induction, yet insights are scarce concerning the free energy of activation within B-DNA. We resort to multiscale simulations to investigate the attack of a hydroxyl radical and of the primary diazonium onto a guanine embedded in a solvated dodecamer. Reaction free energy profiles characterize two strongly exergonic processes, yet allow unprecedented quantification of the barrier towards this damage reaction, not higher than 6 kcal mol−1 and sometimes inexistent, and of the exergonicities. In the case of the [G(C8)-OH]˙ intermediate, we challenge the functional dependence of such simulations…
Ultrastructural Alterations of Midgut Epithelium, but Not Greater Wing Fluctuating Asymmetry, in Paper Wasps (Polistes dominula) from Urban Environme…
2018
Polistes paper wasps can be used to monitor trace metal contaminants, but the effects of pollution on the health of these insects are still unknown. We evaluated, in a south-eastern area of Spain, whether workers of Polistes dominula collected at urban and rural sites differ in health of midgut tissue and in fluctuating asymmetry, an estimate of developmental noise. We found that wasps collected at the urban sites had abundant lead (Pb)-containing spherites, which were less visible in wasps from the rural sites. Evident ultrastructural alterations in the epithelium of the midgut of the wasps collected at the urban sites included broken and disorganized microvilli, a high amount and density …
DNA damage and repair in the differentiation of stem cells and cells of connective cell lineages: A trigger or a complication?
2021
The review summarizes literature data on the role of DNA breaks and DNA repair in differentiation of pluripotent stem cells (PSC) and connective cell lineages. PSC, including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC), are rapidly dividing cells with highly active DNA damage response (DDR) mechanisms to ensure the stability and integrity of the DNA. In PSCs, the most common DDR mechanism is error-free homologous recombination (HR) that is primarily active during S phase of the cell cycle, whereas in quiescent, slow-dividing or non-dividing tissue progenitors and terminally differentiated cells, error-prone non-homologous end joining (NHEJ) mechanism of the double-s…
N-(2-methyl-indol-1H-5-yl)-1-naphthalenesulfonamide : a novel reversible antimitotic agent inhibiting cancer cell motility
2016
Este es el post-print que se ha publicado de forma definitiva en: https://www.sciencedirect.com/science/article/abs/pii/S0006295216301423 A series of compounds containing the sulfonamide scaffold were synthesized and screened for their in vitro anticancer activity against a representative panel of human cancer cell lines, leading to the identification of N-(2-methyl-1H-indol-5-yl)-1-naphthalenesulfonamide (8e) as a compound showing a remarkable activity across the panel, with IC50 values in the nanomolar-to-low micromolar range. Cell cycle distribution analysis revealed that 8e promoted a severe G2/M arrest, which was followed by cellular senescence as indicated by the detection of senescen…
Molecular Biology of Atherosclerotic Ischemic Strokes
2020
Among the causes of global death and disability, ischemic stroke (also known as cerebral ischemia) plays a pivotal role, by determining the highest number of worldwide mortality, behind cardiomyopathies, affecting 30 million people. The etiopathogenetic burden of a cerebrovascular accident could be brain ischemia (~80%) or intracranial hemorrhage (~20%). The most common site when ischemia occurs is the one is perfused by middle cerebral arteries. Worse prognosis and disablement consequent to brain damage occur in elderly patients or affected by neurological impairment, hypertension, dyslipidemia, and diabetes. Since, in the coming years, estimates predict an exponential increase of people w…
Exposure to environmental radionuclides alters mitochondrial DNA maintenance in a wild rodent
2020
AbstractMitochondria are sensitive to oxidative stress, including that derived from ionizing radiation. To quantify the effects of exposure to environmental radionuclides on mitochondrial DNA (mtDNA) dynamics in wildlife, bank voles (Myodes glareolus) were collected from the chernobyl exclusion zone (CEZ), where animals are exposed to elevated levels of radionuclides, and from uncontaminated areas within the CEZ and elsewhere in Ukraine. Brains of bank voles from outside the CEZ were characterized by low mtDNA copy number and low mtDNA damage; by contrast, bank voles within the CEZ had high mtDNA copy number and high mtDNA damage, consistent with putative damaging effects of elevated radiat…
Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
2020
Abstract Background Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. Methods Fibroblasts from skin biopsies of…