One of the most basic functions in any organism is DNA repair. In addition, programmed DNA "damage," in the form of DNA double-strand breaks (DSBs), is a regular part of the physiology of most organisms. There are three main types of DSB repair: homologous recombination; single-strand annealing; and nonhomologous end joining. The gene products known to be required for these repair processes are conserved in evolution, but the relative dependence on different pathways for DSB repair is different when systems are compared. In the yeast Saccharomyces cerevisiae, the formation and repair of DNA double-strand breaks (DSBs) is apparently an essential feature of meiotic recombination. However, it is not clear whether DSBs are a conserved feature of meiotic recombination in eukaryotes. The basidiomycete Coprinus cinereus presents an experimental system which is amenable to genetic analysis, processes DSBs in a manner similar to complex eukaryotes, and has a naturally synchronous meiosis. An understanding of the functions of conserved genes in DSB repair in C. cinereus and other similar systems will help to determine whether DSB repair is a unifying theme in meiotic recombination or whether conserved gene products have other essential functions that tie together DNA repair and meiosis.
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http://dx.doi.org/10.1016/s0070-2153(08)60173-8 | 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 PDFNat Commun
January 2025
Crick-GSK Biomedical LinkLabs, GSK, Gunnels Wood Road, Stevenage, Hertfordshire, UK.
Identifying pharmacological probes for human proteins represents a key opportunity to accelerate the discovery of new therapeutics. High-content screening approaches to expand the ligandable proteome offer the potential to expedite the discovery of novel chemical probes to study protein function. Screening libraries of reactive fragments by chemoproteomics offers a compelling approach to ligand discovery, however, optimising sample throughput, proteomic depth, and data reproducibility remains a key challenge.
View Article and Find Full Text PDFRadiat Res
December 2024
Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, Germany.
It is thought that cells surviving ionizing radiation exposure repair DNA double-strand breaks (DSBs) and restore their genomes. However, the recent biochemical and genetic characterization of DSB repair pathways reveals that only homologous recombination (HR) can function in an error-free manner and that the non-homologous end joining (NHEJ) pathways canonical NHEJ (c-NHEJ), alternative end joining (alt-EJ), and single-strand annealing (SSA) are error-prone, and potentially leave behind genomic scars and altered genomes. The strong cell cycle restriction of HR to S/G2 phases and the unparalleled efficiency of c-NHEJ throughout the cell cycle, raise the intriguing question as to how far a surviving cell "reaches" after repairing the genome back to its pre-irradiation state.
View Article and Find Full Text PDFCurr Opin Pharmacol
December 2024
Biotechnology Research and Innovation Council - National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India; Biotechnology Research and Innovation Council - National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani 741251, India. Electronic address:
DNA damage signaling is a highly coordinated cellular process which is required for the removal of DNA lesions. Amongst the different types of DNA damage, double-strand breaks (DSBs) are the most harmful type of lesion that attenuates cellular proliferation. DSBs are repaired by two major pathways-homologous recombination (HR), and non-homologous end-joining (NHEJ) and in some cases by microhomology-mediated end-joining (MMEJ).
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