Homologous recombination among repetitive sequences is an important mode of DNA repair in eukaryotes following acute radiation exposure. We have developed an assay in Saccharomyces cerevisiae that models how multiple DNA double-strand breaks form chromosomal translocations by a nonconservative homologous recombination mechanism, single-strand annealing, and identified the Rad52 paralog, Rad59, as an important factor. We show through genetic and molecular analyses that Rad59 possesses distinct Rad52-dependent and -independent functions, and that Rad59 plays a critical role in the localization of Rad52 to double-strand breaks. Our analysis further suggests that Rad52 and Rad59 act in multiple, sequential processes that determine genome structure following acute exposure to DNA damaging agents.
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http://dx.doi.org/10.1002/mbo3.31 | DOI Listing |
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.
View Article and Find Full Text PDFAlzheimers Dement
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.
View Article and Find Full Text PDFInt J Radiat Biol
January 2025
N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
Background: Enumeration of residual DNA repair foci 24 hours or more after exposure to ionizing radiation (IR) is often used to assess the efficiency of DNA double-strand break repair. However, the relationship between the number of residual foci in irradiated cells and the radiation dose is still poorly understood. The aim of this work was to investigate the dose responses for residual DNA repair foci in normal human fibroblasts after X-ray exposure in the absorbed dose range from 0.
View Article and Find Full Text PDFProstate
January 2025
Radiation and Cancer Therapeutics Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Background: Caffeic acid (CA), a dietary compound, has been studied for its potential impact on inhibiting prostate cancer (PCa) growth. PCa is often associated with heightened expression of glyoxalase-1 (Glo-1), making it a target for potential therapeutic interventions. CA's mechanisms in suppressing Glo-1 expression and its effects on PCa cell proliferation are areas of interest for understanding its potential as an anticancer agent.
View Article and Find Full Text PDFEMBO Rep
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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