We examined frequencies of radiation-induced chromosomal aberrations, using classical cytological methods, and DNA damage in interphase and metaphase cells, using a combination of FISH, CO-FISH, TIF (telomere dysfunction induced assay) and simultaneous detection of DNA damage and telomeric sequences in metaphase chromosomes, in Chinese hamster cells defective in BRCA2 and control cells. Given that the Chinese hamster genome contains large blocks of interstitial telomeric sites, our results allow us to examine the role of BRCA2 in the potential fragility of these sites, but also whether BRCA2 affects DNA repair within terminal telomeric sequences. BRCA2 defective cells exhibited greater frequencies of DNA damage within interstitial telomeric sites, as well as within terminal telomeric sites, relative to control cells. Therefore, BRCA2 deficiency contributes to the telomere dysfunction phenotype in Chinese hamster cells.
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http://dx.doi.org/10.1016/j.mrgentox.2022.503476 | DOI Listing |
Sci Adv
January 2025
Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, Louisiana Cancer Research Center, 1700 Tulane Avenue, New Orleans, LA 70112, USA.
Unlike most species that use telomerase for telomere maintenance, many dipterans, including , rely on three telomere-specific retrotransposons (TRs)-, , and -to form tandem repeats at chromosome ends. Although TR transcription is crucial in their life cycle, its regulation remains poorly understood. This study identifies the Mediator complex, E2F1-Dp, and Scalloped/dTEAD as key regulators of TR transcription.
View Article and Find Full Text PDFFEBS Lett
December 2024
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Genome maintenance is essential for the integrity of the genetic blueprint, of which only a small fraction is transcribed in higher eukaryotes. DNA lesions occurring in the transcribed genome trigger transcription pausing and transcription-coupled DNA repair. There are two major transcription-coupled DNA repair pathways.
View Article and Find Full Text PDFClin Epigenetics
December 2024
Third Department of Internal Medicine, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata, Osaka, 573-1010, Japan.
Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) progression sequence and its association with host genotoxic changes. 16S rRNA gene sequencing was performed in three different groups of biopsies from nonneoplastic BE from patients without cancer (N, normal group; n = 47) and with EAC (ADJ, adjacent group; n = 27).
View Article and Find Full Text PDFSci Rep
December 2024
Quantitative Proteomics, Institute of Molecular Biology (IMB), 55128, Mainz, Germany.
The extracellular parasite Trypanosoma brucei evades the immune system of the mammalian host by periodically exchanging its variant surface glycoprotein (VSG) coat. Hereby, only one VSG gene is transcribed from one of 15 subtelomeric so-called bloodstream form expression sites (BES) at any given timepoint, while all other BESs are silenced. VSG gene expression is altered by homologous recombination using a large VSG gene repertoire or by a so-called in situ switch, which activates a previously silent BES.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Biology and Epigenetics Institute, University of Pennsylvania, Philadelphia, PA.
Many essential conserved functions depend, paradoxically, on proteins that evolve rapidly under positive selection. How such adaptively evolving proteins promote biological innovation while preserving conserved, essential functions remains unclear. Here, we experimentally test the hypothesis that adaptive protein-protein coevolution within an essential multi-protein complex mitigates the deleterious incidental byproducts of innovation under pressure from selfish genetic elements.
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