ArticleDNA repair2014
High levels of BRC4 induced by a Tet-On 3G system suppress DNA repair and impair cell proliferation in vertebrate cells.
Article in DNA repair, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Application of neural network-based image analysis to detect sister chromatid cohesion defects.Scientific reports · 2023Article
- Dipeptidyl peptidase 9 triggers BRCA2 degradation and promotes DNA damage repair.EMBO reports · 2022Article
- Vertebrate CTF18 and DDX11 essential function in cohesion is bypassed by preventing WAPL-mediated cohesin release.Genes & development · 2021Article
- Targeting chromosome trisomy for chromosome editing.Scientific reports · 2021Article
- Correlation of homologous recombination deficiency induced mutational signatures with sensitivity to PARP inhibitors and cytotoxic agents.Genome biology · 2019Article
- Phosphorylation of proliferating cell nuclear antigen promotes cancer progression by activating the ATM/Akt/GSK3β/Snail signaling pathway.The Journal of biological chemistry · 2019Article
- Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- AND-1 fork protection function prevents fork resection and is essential for proliferation.Nature communications · 2018Article
- ESCO1/2's roles in chromosome structure and interphase chromatin organization.Genes & development · 2017Article
- A double-strand break can trigger immunoglobulin gene conversion.Nucleic acids research · 2017Article
- Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion.Oncotarget · 2016Article
- Molding BRCA2 function through its interacting partners.Cell cycle (Georgetown, Tex.) · 2015Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Transient induction or suppression of target genes is useful to study the function of toxic or essential genes in cells. Here we apply a Tet-On 3G system to DT40 lymphoma B cell lines, validating it for three different genes. Using this tool, we then show that overexpression of the chicken BRC4 repeat of the tumor suppressor BRCA2 impairs cell proliferation and induces chromosomal breaks. Mechanistically, high levels of BRC4 suppress double strand break-induced homologous recombination, inhibit the formation of RAD51 recombination repair foci, reduce cellular resistance to DNA damaging agents and induce a G2 damage checkpoint-mediated cell-cycle arrest. The above phenotypes are mediated by BRC4 capability to bind and inhibit RAD51. The toxicity associated with BRC4 overexpression is exacerbated by chemotherapeutic agents and reversed by RAD51 overexpression, but it is neither aggravated nor suppressed by a deficit in the non-homologous end-joining pathway of double strand break repair. We further find that the endogenous BRCA2 mediates the cytotoxicity associated with BRC4 induction, thus underscoring the possibility that BRC4 or other domains of BRCA2 cooperate with ectopic BRC4 in regulating repair activities or mitotic cell division. In all, the results demonstrate the utility of the Tet-On 3G system in DT40 research and underpin a model in which BRC4 role on cell proliferation and chromosome repair arises primarily from its suppressive role on RAD51 functions.
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