Mitotic homologous recombination promotes genome stability through the precise repair of DNA double-strand breaks and other lesions that are encountered during normal cellular metabolism and from exogenous insults. As a result, homologous recombination repair is essential during proliferative stages in development and during somatic cell renewal in adults to protect against cell death and mutagenic outcomes from DNA damage. Mutations in mammalian genes encoding homologous recombination proteins, including BRCA1, BRCA2 and PALB2, are associated with developmental abnormalities and tumorigenesis. Recent advances have provided a clearer understanding of the connections between these proteins and of the key steps of homologous recombination and DNA strand exchange.
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http://dx.doi.org/10.1038/nrm2851 | DOI Listing |
Alternative Lengthening of Telomeres (ALT) is a homologous recombination-dependent telomere elongation mechanism utilized by at least 10-15% of all cancers. Here we identified that the DNA topoisomerase, TOP3A is enriched at the telomeres of ALT cells but not at the telomeres of telomerase-positive (Tel) cancer cells. We demonstrate that TOP3A stabilizes the shelterin protein TERF2 in ALT cancer cell lines but not in Tel cells and that long non-coding telomere transcribed RNA (TERRA) enrichment at telomeres depends upon TOP3A.
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 PDFJ Genet Genomics
January 2025
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Research Institute, Beijing 100142, China. Electronic address:
Acral melanoma, the most common melanoma subtype in East Asia, is associated with a poor prognosis. This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians. We conduct whole-genome sequencing of 55 acral melanoma tumors and perform data mining with relevant clinical data.
View Article and Find Full Text PDFMol Diagn Ther
January 2025
Istituto Europeo di Oncologia, IRCCS, Via Adamello 16, 20139, Milan, Italy.
Background: Predicting response to targeted cancer therapies increasingly relies on both simple and complex genetic biomarkers. Comprehensive genomic profiling using high-throughput assays must be evaluated for reproducibility and accuracy compared with existing methods.
Methods: This study is a multicenter evaluation of the Oncomine™ Comprehensive Assay Plus (OCA Plus) Pan-Cancer Research Panel for comprehensive genomic profiling of solid tumors.
Nucleic Acids Res
January 2025
MOE Key Laboratory of Biosystems Homeostasis and Protection, College of Life Sciences, Zhejiang University, No.866 Yuhangtang Road, 310058, Hangzhou, China.
Meiosis in mammalian oocytes is interrupted by a prolonged arrest at the germinal vesicle stage, during which oocytes have to repair DNA lesions to ensure genome integrity or otherwise undergo apoptosis. The FIRRM/FLIP-FIGNL1 complex dissociates RAD51 from the joint DNA molecules in both homologous recombination (HR) and DNA replication. However, as a type of non-meiotic, non-replicative cells, whether this RAD51-dismantling mechanism regulates genome integrity in oocytes remains elusive.
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