ArticleInternational journal of biological sciences2016
"DNA Binding Region" of BRCA1 Affects Genetic Stability through modulating the Intra-S-Phase Checkpoint.
Article in International journal of biological sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Novel driver gene FIRRM regulates the cell cycle for promoting tumor growth in hepatocellular carcinoma.Journal of gastroenterology · 2026Article
- A report of novel inactivating missense mutations of BRCA1 detected in patients with acute myeloid leukemia.Journal of medical case reports · 2026Article
- ZNF282 Promotes Colorectal Cancer Progression Possibly via E2F1 Activation.Cancer science · 2026Article
- Cytotoxic Anti-tumor Drugs and Tumor-Associated Macrophages Synergistically Surge PD-L1 Expression in Esophageal Squamous Cell Carcinoma.Annals of surgical oncology · 2025Article
- Domain-Specific DNA Binding Activities of BRCA1 Reveal Substrate Preferences for Homologous Recombination and Telomere Regulation.Biochemistry · 2025Article
- Coordinated protein modules define DNA damage responses to carboplatin at single-cell resolution in human ovarian carcinoma models.Cell reports. Medicine · 2025Article
- Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression.Cancer science · 2025Article
- SEC61G promotes colorectal cancer progression by regulating cytosolic CaJournal of gastroenterology · 2025Article
- SET-binding protein 1 (SETBP1) suppresses cell proliferation in estrogen receptor-positive breast cancer.Breast cancer (Tokyo, Japan) · 2025Article
- Tumor suppressive role of the epigenetic master regulator BRD3 in colorectal cancer.Cancer science · 2024Article
- Transducin Beta-Like 2 is a Potential Driver Gene that Adapts to Endoplasmic Reticulum Stress to Promote Tumor Growth of Lung Adenocarcinoma.Annals of surgical oncology · 2023Article
- BRCA1 the Versatile Defender: Molecular to Environmental Perspectives.International journal of molecular sciences · 2023Review
- BRCA1/BARD1 intrinsically disordered regions facilitate chromatin recruitment and ubiquitylation.The EMBO journal · 2023Article
- BRCA1/BARD1 site-specific ubiquitylation of nucleosomal H2A is directed by BARD1.Nature structural & molecular biology · 2021Article
- BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Nano-scientific Application of Atomic Force Microscopy in Pathology: from Molecules to Tissues.International journal of medical sciences · 2020Review
- TheGenes · 2019Article
- How to Choose a Mouse Model of Breast Cancer, a Genomic Perspective.Journal of mammary gland biology and neoplasia · 2019Review
- BRCA1 represses DNA replication initiation through antagonizing estrogen signaling and maintains genome stability in parallel with WEE1-MCM2 signaling during pregnancy.Human molecular genetics · 2019Article
- BRCA1 function in the intra-S checkpoint is activated by acetylation via a pCAF/SIRT1 axis.Oncogene · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The breast cancer associated gene 1 (BRCA1) contains 3 domains: an N-terminal RING domain with ubiquitin E3 ligase activity, C-terminal BRCT protein interaction domain and a central region. RING and BRCT domains are well characterized, yet the function of the central region remains unclear. In this study, we identified an essential DNA binding region (DBR: 421-701 amino acids) within the central region of human BRCA1, and found that BRCA1 brings DNA together and preferably binds to splayed-arm DNA in a sequence-independent manner. To investigate the biological role of the DBR, we generated mouse ES cells, which lack the DBR (ΔDBR) by using the TALEN method. The ΔDBR cells exhibited decreased survival as compared to the wild type (WT) cells treated with a PARP inhibitor, however they have an intact ability to conduct DNA repair mediated by homologous recombination (HR). The ΔDBR cells continued to incorporate more EdU in the presence of hydroxyurea (HU), which causes replication stress and exhibited reduced viability than the WT cells. Moreover, phosphorylation of CHK1, which regulates the intra-S phase checkpoint, was moderately decreased in ΔDBR cells. These data suggest that DNA binding by BRCA1 affects the stability of DNA replication folks, resulting in weakened intra-S-phase checkpoint control in the ΔDBR cells. The ΔDBR cells also exhibited an increased number of abnormal chromosome structures as compared with WT cells, indicating that the ΔDBR cells have increased genetic instability. Thus, we demonstrated that the DBR of BRCA1 modulates genetic stability through the intra-S-phase checkpoint activated by replication stress.
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