The clastogenic effects on DNA, proven by the presence of micronuclei (MN), and the protective cellular mechanisms normally used to stabilize DNA breaks were investigated in patients with systemic sclerosis (SSc). The frequency of micronucleated cells found in cultures of peripheral lymphocytes in patients was significantly higher than in the control group. The patient group with anti-centromere antibodies showed a significantly higher frequency of micronucleated cells than that observed in the patients with anti-topoisomerase I antibodies (4.22% versus 2.34%, p < 0.001). Moreover, we attempted to characterize MN for the presence or absence of DNA fragments with free 3'-OH ends by digoxigenin-dUTP (DIG-dUTP) using terminal deoxynucleotidil transferase. It was found that the frequency of MN containing DNA fragments with 3'-OH free ends (unstable fragments) increased in SSc patients compared to that observed in the control group. Moreover, this increase was significantly higher in lymphocytes of the patients with anti-centromere antibodies than in those with anti-topoisomerase I antibodies (35% versus 20.08%, p < 0.001). Our results indicate that in SSc patients there is an interference in the protective cellular mechanisms, normally stabilizing DNA breaks.
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Alzheimers Dement
December 2024
University of Pennsylvania, Philadelphia, PA, USA.
Background: To date, Alzheimer's disease (AD) research has principally focused on neurons. In contrast, recent studies suggest that genetic mechanisms drive microglia towards prolonged inflammation in AD brains, exacerbating neurodegeneration. Indeed, many of the 70 disease-associated loci uncovered with genome-wide association studies (GWAS) reside near genes related to microglial function, such as TREM2.
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December 2024
University of Tennessee Health Science Center, Memphis, TN, USA.
Background: Tauopathies are a group of neurological disorders including Alzheimer's disease that involve progressive neurodegeneration, behavioral deficits, and aberrant tau accumulation. While the molecular mechanisms that regulate the progression of the tauopathy are not fully elucidated, there is evidence to suggest that accumulation of nuclear DNA damage, particularly nuclear DNA double-strand breaks (DNA DSBs), contribute to the progression of neurodegeneration. In our present work, we investigated the relationship between DNA DSB accumulation and neuroinflammation in the brains of AD patients and a mouse model of tauopathy.
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January 2025
Radiation and Cancer Therapeutics Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
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January 2025
Université de Strasbourg, CNRS, GMGM UMR 7156, Strasbourg, France.
Genomic instability is a hallmark of tumorigenesis, yet it also plays an essential role in evolution. Large-scale population genomics studies have highlighted the importance of loss of heterozygosity (LOH) events, which have long been overlooked in the context of genetic diversity and instability. Among various types of genomic mutations, LOH events are the most common and affect a larger portion of the genome.
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January 2025
Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Tumor suppressor BRCA2 executes homologous recombination to repair DNA double-strand breaks in collaboration with RAD51, involving exon 11 and 27. Exon 11 constitutes a region where pathogenic variants (PVs) accumulate, and mutations in this region are known to contribute to carcinogenesis. However, the impact of the heterozygous PVs of BRCA2 exon 11 on the life quality beyond cancer risk, including male fertility, remains unclear.
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