ArticleAging2011
Mutations in the BRCT binding site of BRCA1 result in hyper-recombination.
Article in Aging, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Review
- WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer.Cancer gene therapy · 2023Article
- ABRAXAS1 orchestrates BRCA1 activities to counter genome destabilizing repair pathways-lessons from breast cancer patients.Cell death & disease · 2023Article
- Regulation of DNA damage response by trimeric G-proteins.iScience · 2023Article
- Wwox Binding to the Murine Brca1-BRCT Domain Regulates Timing of Brip1 and CtIP Phospho-Protein Interactions with This Domain at DNA Double-Strand Breaks, and Repair Pathway Choice.International journal of molecular sciences · 2022Article
- Two redundant ubiquitin-dependent pathways of BRCA1 localization to DNA damage sites.EMBO reports · 2021Article
- RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation.Molecular cell · 2019Article
- The Cancer/Testes (CT) Antigen HORMAD1 promotes Homologous Recombinational DNA Repair and Radioresistance in Lung adenocarcinoma cells.Scientific reports · 2018Article
- Synthetically Lethal BMN 673 (Talazoparib) Loaded Solid Lipid Nanoparticles for BRCA1 Mutant Triple Negative Breast Cancer.Pharmaceutical research · 2018Article
- Low- and High-LET Ionizing Radiation Induces Delayed Homologous Recombination that Persists for Two Weeks before Resolving.Radiation research · 2017Article
- Molecular Analysis of BRCA1 in Human Breast Cancer Cells Under Oxidative Stress.Scientific reports · 2017Article
- Expression of cancer related BRCA1 missense variants decreases MMS-induced recombination in Saccharomyces cerevisiae without altering its nuclear localization.Cell cycle (Georgetown, Tex.) · 2016Article
- Ovarian Cancer and BRCA1/2 Testing: Opportunities to Improve Clinical Care and Disease Prevention.Frontiers in oncology · 2016Review
- ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry.PloS one · 2016Article
- Nuclear domain 'knock-in' screen for the evaluation and identification of small molecule enhancers of CRISPR-based genome editing.Nucleic acids research · 2015Article
- Article
- Peptide library approach to uncover phosphomimetic inhibitors of the BRCA1 C-terminal domain.ACS chemical biology · 2015Article
- Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins.Cold Spring Harbor perspectives in biology · 2015Review
- BRCA1 functions as a novel transcriptional cofactor in HIV-1 infection.Virology journal · 2015Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
We introduced a K1702M mutation in the BRCA1 BRCT domain known to prevent the binding of proteins harboring pS-X-X-F motifs such as Abraxas-RAP80, BRIP1, and CtIP. Surprisingly, rather than impairing homologous recombination repair (HRR), expression of K1702M resulted in hyper-recombination coinciding with an accumulation of cells in S-G2 and no effect on nonhomologous end-joining. These cells also showed increased RAD51 and RPA nuclear staining. More pronounced effects were seen with a naturally occurring BRCT mutant (M1775R) that also produced elevated levels of ssDNA, in part co-localizing with RPA, in line with excessive DNA resection. M1775R induced unusual, thread-like promyelocytic leukemia (PML) nuclear bodies and clustered RPA foci rather than the typical juxtaposed RPA-PML foci seen with wild-type BRCA1. Interestingly, K1702M hyper-recombination diminished with a second mutation in the BRCA1 RING domain (I26A) known to reduce BRCA1 ubiquitin-ligase activity. Thesein vitro findings correlated with elevated nuclear RAD51 and RPA staining of breast cancer tissue from a patient with the M1775R mutation. Altogether, the disruption of BRCA1 (BRCT)-pS-X-X-F protein binding results in ubiquitination-dependent hyper-recombination via excessive DNA resection and the appearance of atypical PML-NBs. Thus, certain BRCA1 mutations that cause hyper-recombination instead of reduced DSB repair might lead to breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.