DNA double-strand break (DSB) repair by homologous recombination (HR) uses a DNA template with similar sequence to restore genetic identity. Allelic DNA repair templates can be found on the sister chromatid or homologous chromosome. During meiotic recombination, DSBs preferentially repair from the homologous chromosome, with a proportion of HR events generating crossovers. Nevertheless, regions of similar DNA sequence exist throughout the genome, providing potential DNA repair templates. When DSB repair occurs at these non-allelic loci (termed ectopic recombination), chromosomal duplications, deletions and rearrangements can arise. Here, we characterize in detail ectopic recombination arising between a dispersed pair of inverted repeats in wild-type Saccharomyces cerevisiae at both a local and a chromosomal scale-the latter identified via gross chromosomal acentric and dicentric chromosome rearrangements. Mutation of the DNA damage checkpoint clamp loader Rad24 and the RecQ helicase Sgs1 causes an increase in ectopic recombination. Unexpectedly, additional mutation of the RecA orthologues Rad51 and Dmc1 alters-but does not abolish-the type of ectopic recombinants generated, revealing a novel class of inverted chromosomal rearrangement driven by the single-strand annealing pathway. These data provide important insights into the role of key DNA repair proteins in regulating DNA repair pathway and template choice during meiosis.
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http://dx.doi.org/10.1093/nar/gkad650 | DOI Listing |
PLoS Pathog
January 2025
State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Medical School, Wuhan University, Wuhan, China.
Chronic hepatitis B virus (HBV) infection can significantly increase the incidence of cirrhosis and liver cancer, and there is no curative treatment. The persistence of HBV covalently closed circular DNA (cccDNA) is the major obstacle of antiviral treatments. cccDNA is formed through repairing viral partially double-stranded relaxed circular DNA (rcDNA) by varies host factors.
View Article and Find Full Text PDFCell Rep
January 2025
Laboratory of Biochemistry, Wageningen University, 6708 WE Wageningen, the Netherlands. Electronic address:
Bacteria encode various DNA repair pathways to maintain genome integrity. However, the high degree of homology between DNA repair proteins or their domains hampers accurate identification. Here, we describe a stringent search strategy to identify DNA repair proteins and provide a systematic analysis of taxonomic distribution and co-occurrence of DNA repair proteins involved in RecA-dependent homologous recombination.
View Article and Find Full Text PDFArch Toxicol
January 2025
Institute of Life Science, Swansea University Medical School, Swansea, UK.
The tumorigenic dose 50 (TD) is a widely used measure of carcinogenic potency which has historically been used to determine acceptable intake limits for carcinogenic compounds. Although broadly used, the TD model was not designed to account for important biological factors such as DNA repair and cell compensatory mechanisms, changes in absorption, etc., leading to the development of benchmark dose (BMD) approaches, which use more flexible dose-response models that are better able to account for these processes.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background: Various studies indicated that the immune system is a cardinal feature of Alzheimer's disease (AD), which can either ameliorate or exacerbate AD neuropathogenesis. Nevertheless, the associations between genes involved in the immune system and AD remain unclear.
Method: To systematically evaluate the associations of these genes with AD, we investigated 370 genes implicated in the immune system based on previous studies selected using the PubMed database.
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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