DNA double-strand breaks (DSBs) are, arguably, the most deleterious form of DNA damage. An increasing body of evidence points to the inaccurate or inefficient repair of DSBs as a key step in tumorigenesis. Therefore, it is of great importance to understand the processes by which DSBs are detected and repaired. Clearly, these events must take place in the context of chromatin in vivo, and recently, a great deal of progress has been made in understanding the dynamic and active role that histone proteins and chromatin modifying activities play in DNA DSB repair. Here, we briefly review some of the most common techniques in studying DNA DSB responses in vivo, and focus on the contributions of covalent modifications of core histone proteins to these DNA DSB responses.
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http://dx.doi.org/10.1093/mutage/gei031 | 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 PDFG-quadruplexes (G4s) are four-stranded alternative secondary structures formed by guanine-rich nucleic acids and are prevalent across the human genome. G4s are enzymatically resolved using specialized helicases. Previous studies showed that DEAH-box Helicase 36 (DHX36/G4R1/RHAU), has the highest specificity and affinity for G4 structures.
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.
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