Aging may be characterized as the progressive increase of the risk of death caused by a decrease of almost all bodily functions. While a great number of model organism studies have established the role of DNA double strand breaks (DSBs) as one of the main causes of aging, few studies have examined whether common polymorphisms in human DSB repair genes influence aging and mortality. More importantly, to the best of our knowledge, no longitudinal study has thus far examined the link between polymorphisms in DSB repair and the risk of death. This longitudinal study thus analyses whether four common polymorphisms (rs2155209, rs7963551, rs17105278, rs2735383) in four selected DSB repair genes (MRE11A, RAD52, RAD51B, NBS1) influence the hazard of age-adjusted death in a cohort of patients with typical symptoms of ischemic heart disease. The results have shown that rs7963551 G/T heterozygotes exhibit a significantly increased hazard of death when compared with the combined GG and TT homozygotes (HR=1.42, 95% CI: 1.06-1.91, p=0.018). This study indicates that the SNP affecting efficiency of DSB repair may influence aging in humans.
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http://dx.doi.org/10.1016/j.mad.2017.10.003 | DOI Listing |
Nat Cell Biol
January 2025
Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.
Double-strand breaks (DSBs) can initiate mitotic catastrophe, a complex oncosuppressive phenomenon characterized by cell death during or after cell division. Here we unveil how cell cycle-regulated DSB repair guides disparate cell death outcomes through single-cell analysis of extended live imaging. Following DSB induction in S or G2, passage of unresolved homologous recombination intermediates into mitosis promotes non-immunogenic intrinsic apoptosis in the immediate attempt at cell division.
View Article and Find Full Text PDFStructural variations (SVs) play important roles in genetic diversity, evolution, and carcinogenesis and are, as such, important for human health. However, it remains unclear how spatial proximity of double-strand breaks (DSBs) affects the formation of SVs. To investigate if spatial proximity between two DSBs affects DNA repair, we used data from 3C experiments (Hi-C, ChIA-PET, and ChIP-seq) to identify highly interacting loci on six different chromosomes.
View Article and Find Full Text PDFHeliyon
January 2025
Instituto de Bioingeniería, Universidad Miguel Hernández, Campus de Elche, 03202, Elche, Spain.
The human deoxyribonucleoside triphosphatase (dNTPase) Sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1) has a dNTPase-independent role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Here, we show that VENOSA4 (VEN4), the probable ortholog of SAMHD1, also functions in DSB repair by HR. The loss-of-function mutants showed increased DNA ploidy and deregulated DNA repair genes, suggesting DNA damage accumulation.
View Article and Find Full Text PDFCytokine Growth Factor Rev
January 2025
Center for Precision Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Pathology, College of Medicine, China Medical University, Taichung, Taiwan. Electronic address:
Receptor tyrosine kinases (RTKs) are membrane sensors that monitor alterations in the extracellular milieu and translate this information into appropriate cellular responses. Epidermal growth factor receptor (EGFR) is the most well-known model in which gene expression is upregulated by mitogenic signals through the activation of multiple signaling cascades or by nuclear translocation of the full-length EGFR protein. RON (Receptuer d'Origine Nantatise, also known as macrophage stimulating 1 receptor, MST1R) has recently gained attention as a therapeutic target for human cancer.
View Article and Find Full Text PDFGenetics
January 2025
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Bloom Syndrome helicase (Blm) is a RecQ family helicase involved in DNA repair, cell-cycle progression, and development. Pathogenic variants in human BLM cause the autosomal recessive disorder Bloom Syndrome, characterized by predisposition to numerous types of cancer. Prior studies of Drosophila Blm mutants lacking helicase activity or protein have shown sensitivity to DNA damaging agents, defects in repairing DNA double-strand breaks (DSBs), female sterility, and improper segregation of chromosomes in meiosis.
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