BRCA1 is closely related to the pathogenesis of breast cancer. The activity of BRCA1 promoter is regulated by transcriptional factors. The transcription factor Nrf2 (Nuclear factor-erythroid-2p45-related factor 2) is a potent transcriptional activator and plays a central role in inducible expression of many cytoprotective genes. In this report, we found that over-expression of Nrf2 stimulated BRCA1 expression, knockdown of Nrf2 attenuated BRCA1 expression. Nrf2 also interacted with CBP and p300 to form an active transcription complex, which could bind to the ARE (antioxidant response element) site on the BRCA1 promoter and activate its transcription by inducing histone acetylation. Our finding could lead to a better understanding of the development of breast cancer.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1093/abbs/gmt001 | DOI Listing |
Mol Cancer Ther
January 2025
Tango Therapeutics (United States), Boston, United States.
Synthetic lethality approaches in BRCA1/2-mutated cancers have focused on poly(ADP-ribose) polymerase (PARP) inhibitors, which are subject to high rates of innate or acquired resistance in patients. Here, we used CRISPR/Cas9-based screening to identify DNA Ligase I (LIG1) as a novel target for synthetic lethality in BRCA1-mutated cancers. Publicly available data supported LIG1 hyperdependence of BRCA1-mutant cells across a variety of breast and ovarian cancer cell lines.
View Article and Find Full Text PDFNat Commun
January 2025
Robson DNA Science Centre, Charbonneau Cancer Institute, Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.
View Article and Find Full Text PDFACS Sens
January 2025
Department of Clinical Laboratory of Sir Run Run Shaw Hospital, College of Biosystems Engineering and Food Science, Zhejiang University School of Medicine, Hangzhou 310058, People's Republic of China.
The rapid, simple, and sensitive detection of nucleic acid biomarkers plays a significant role in clinical diagnosis. Herein, we develop a label-free and point-of-care approach for isothermal DNA detection through the trans-cleavage activity of CRISPR-Cas12 and the growth of gold nanomaterials in agarose gel. The presence of the target can activate CRISPR-Cas12a to cleave single-stranded DNA, thus modulating the length and number of DNA sequences that mediate the growth of gold nanoparticles (AuNPs) or gold nanorods (AuNRs).
View Article and Find Full Text PDFProteomes
December 2024
UMR6252 CIMAP, Team Applications in Radiobiology with Accelerated Ions, CEA-CNRS-ENSICAEN, Université de Caen Normandie, 14000 Caen, France.
Glioblastoma (GBM) is a devastating malignant brain tumor with a poor prognosis. GBM is associated with radioresistance. Post-translational modifications (PTMs) such as protein phosphorylation can play an important role in the cellular response to radiation.
View Article and Find Full Text PDFBMC Cancer
January 2025
Medical and Translational Oncology, Department of Oncology, Azienda Ospedaliera Santa Maria, Viale Tristano Di Joannuccio 1, Terni, 05100, Italy.
Prostate cancer (PCa) ranks among the most prevalent malignancies in men, with notable associations to Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Lynch Syndrome, both linked to germline likely pathogenetic variant/pathogenetic variant (LPV/PV) in genes involved in DNA repair. Among these genes, BRCA2 in PCa patients is the most frequently altered. Despite progresses, challenges in BRCA carriers detection persist, with a quarter of PCa cases lacking family history.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!