The E2F1 transcription factor and RB tumor suppressor are best known for their roles in regulating the expression of genes important for cell cycle progression but, they also have transcription-independent functions that facilitate DNA repair at sites of damage. Depending on the type of DNA damage, E2F1 can recruit either the GCN5 or p300/CBP histone acetyltransferases to deposit different histone acetylation marks in flanking chromatin. At DNA double-strand breaks, E2F1 also recruits RB and the BRG1 ATPase to remodel chromatin and promote loading of the MRE11-RAD50-NBS1 complex. Knock-in mouse models demonstrate important roles for E2F1 post-translational modifications in regulating DNA repair and physiological responses to DNA damage. This review highlights how E2F1 moonlights in DNA repair, thus revealing E2F1 as a versatile protein that recruits many of the same chromatin-modifying enzymes to sites of DNA damage to promote repair that it recruits to gene promoters to regulate transcription.
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http://dx.doi.org/10.1080/15384101.2020.1801190 | DOI Listing |
J Occup Environ Med
November 2024
Industrial Medicine and Occupational Health, Public Health and Community Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Objectives: This study aimed to assess mutagenicity biomarkers among Egyptian textile dyeing workers, their alteration with gene polymorphism, and the changes in plasma proteins' expression.
Methods: Using a detailed questionnaire, a comparative cross-sectional study was conducted on 212 workers (106 textile dyeing exposed group and 106 control group). CBMN-Cyt assay, ERCC2 gene polymorphism, and plasma protein fractions were analyzed in workers' blood samples.
Mamm Genome
January 2025
CNRS, INSERM, CELPHEDIA, Institut Clinique de la Souris (ICS), Université de Strasbourg, Illkirch, PHENOMIN, France.
Genome editing, in particular the CRISPR/Cas9 system, is widely used to generate new animal models. However, the generation of mutations, such as conditional knock-out or knock-in, can remain complex and inefficient, in particular because of the difficulty to deliver the donor DNA (single or double stranded) into the nucleus of fertilized oocytes. The use of recombinant adeno-associated viruses (rAAV) as donor DNA is a rapidly developing approach that promises to improve the efficiency of creation of animal models.
View Article and Find Full Text PDFClin Cancer Res
January 2025
The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Purpose: More active high-dose chemotherapy (HDC) regimens are needed for autologous stem-cell transplantation (ASCT) for refractory lymphomas. Seeking HDC enhancement with a poly(ADP-ribose) polymerase (PARP) inhibitor, we observed marked synergy between olaparib and vorinostat/gemcitabine/busulfan/melphalan (GemBuMel) against lymphoma cell lines, mediated by inhibition of DNA damage repair. Our preclinical work led us to clinically study olaparib/vorinostat/GemBuMel with ASCT.
View Article and Find Full Text PDFJ Med Chem
January 2025
Jiangsu Key Laboratory of Drug Design and Optimization and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Targeting the WDR5-MLL1 protein-protein interaction (PPI) is considered to be an effective approach for the treatment of MLL-rearranged leukemia. However, interfering with WDR5-MLL1 PPI reduces methylated H3K4 levels and induces a decline in acetylated H3 levels, which may contribute to the suboptimal cellular efficacy of WDR5 inhibitors. We observed that cotreatment with WDR5-MLL1 PPI and HDAC inhibitors augmented the antiproliferative effect in MV-4-11 cells.
View Article and Find Full Text PDFAm J Cancer Res
December 2024
Department of Epidemiology, University of Florida, College of Public Health and Health Professions and College of Medicine Gainesville, FL, USA.
We investigated if selected polymorphisms in DNA repair genes modify the association between exposure to particulate matter ≤ 10 micron in diameter (PM) and breast cancer (BCa) risk. We included 150,929 postmenopausal women (5,969 with BCa) from UK Biobank, a population-based prospective cohort. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers.
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