Constant exposure to various environmental and endogenous stresses can cause structural DNA damage, resulting in genome instability. Higher eukaryotic cells deploy conserved DNA repair systems, which include various DNA repair pathways, to maintain genome stability. Homologous recombination (HR), one of these repair pathways, involves multiple proteins. BRCA2, one of the proteins in the HR pathway, is of substantial research interest in humans because it is an oncogene. However, the study of this gene is limited due to the lack of availability of homozygous -knockout mutants in mammals, which results in embryonic lethality. has two copies of the homologs: and . Therefore, the single mutants remain nonlethal and fertile in . The homolog, which plays a significant role in the HR pathway of germline cells and during the defense response, is well-studied in . Our study focuses on the functional characterization of the homolog in the somatic cells of , using the homozygous mutant line. The phenotypic differences of mutants were characterized and compared with wild plants. The role of in spontaneous somatic HR (SHR) was studied using the -gus detector line. plants have a 6.3-fold lower SHR frequency than the control detector plants. Expression of four other HR pathway genes, including , , , and , was significantly reduced in mutants. Thus, our findings convey that the homolog plays an important role in maintaining spontaneous SHR rates and has a direct or indirect regulatory effect on the expression of other HR-related genes.
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http://dx.doi.org/10.5114/bta.2023.132773 | DOI Listing |
BJUI Compass
January 2025
Division of Medical Oncology A Policlinico Umberto I Rome Italy.
Background: We present a systematic review and meta-analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor-targeted agent (ARTA) in first- and second-line settings.
Methods: Primary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild-type (HRR-), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second-line setting is also explored.
Resistance to radiotherapy remains a critical barrier in treating colorectal cancer (CRC), particularly in cases of locally advanced rectal cancer (LARC). To identify key kinases involved in CRC radioresistance, we employed a kinase-targeted CRISPR-Cas9 library screen. This approach aimed to identify potential kinase inhibitors as radiosensitizers.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Laboratory of Genome Regeneration, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo113-0032, Japan.
DNA copy number changes via chromosomal rearrangements or the production of extrachromosomal circular DNA. Here, we demonstrate that the histone deacetylase Sir2 maintains the copy number of budding yeast ribosomal RNA gene [ribosomal DNA (rDNA)] by suppressing end resection of DNA double-strand breaks (DSBs) formed upon DNA replication fork arrest in the rDNA and their subsequent homologous recombination (HR)-mediated rDNA copy number changes during DSB repair. Sir2 represses transcription from the regulatory promoter E-pro located near the fork arresting site.
View Article and Find Full Text PDFNat Rev Cancer
January 2025
Translational Oncogenomics Laboratory, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair.
View Article and Find Full Text PDFCancer Genet
January 2025
Department of Chemistry and Biochemistry, The Ohio State University, Marion, USA. Electronic address:
DNA double strand breaks (DSBs) can be generated spontaneously during DNA replication and are repaired primarily by Homologous Recombination (HR). However, efficient repair requires chromatin remodeling to allow the recombination machinery access to the break. TIP60 is a complex conserved from yeast to humans that is required for histone acetylation and modulation of HR activity at DSBs.
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