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- Dubrovska, AnnaUppsala universitet,Ludwiginstitutet för cancerforskning (author)
TGFbeta1/Smad3 counteracts BRCA1-dependent repair of DNA damage
- Article/chapterEnglish2005
Publisher, publication year, extent ...
- 2005-02-14
- Springer Science and Business Media LLC,2005
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:uu-72687
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-72687URI
- https://doi.org/10.1038/sj.onc.1208443DOI
- http://kipublications.ki.se/Default.aspx?queryparsed=id:110979263URI
Supplementary language notes
- Language:English
- Summary in:English &language:-1_t
Part of subdatabase
- SwePubSwePub
Classification
Notes
- Inactivation of the BRCA1 gene has been found to confer susceptibility to early-onset familial breast and ovarian cancers. BRCA1 regulates DNA repair, chromatin remodeling and affects gene transcription. Transforming growth factor-beta (TGFbeta) is a potent regulator of growth, apoptosis and invasiveness of tumor cells, including breast cancer cells. Here we show that Smad3 which is a component of the TGFbeta signaling pathway, forms a complex with BRCA1 in vitro and in vivo. The interaction is mediated by the MH1 domain of Smad3 and the C-terminal part of BRCA1. We observed a co-localization of Smad3 and BRCA1 in nuclear complexes. We also found that TGFbeta1/Smad3 counteracted BRCA1-dependent repair of DNA double-strand breaks in human breast epithelial cells, as evaluated by BRCA1 nuclear foci formation, single-cell gel electrophoresis and cell survival assays. Thus, TGFbeta1/Smad3 suppresses BRCA1-dependent DNA repair in response to a DNA damaging agent.
Subject headings and genre
- Blotting; Western
- Cell Line
- Cell Survival
- DNA Damage
- DNA Repair/*physiology
- DNA-Binding Proteins/*physiology
- Genes; BRCA1
- Humans
- Immunohistochemistry
- Immunoprecipitation
- Research Support; Non-U.S. Gov't
- Trans-Activators/*physiology
- Transcription; Genetic
- Transforming Growth Factor beta/*physiology
- MEDICINE
- MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
- Kanamoto, TakashiUppsala universitet,Ludwiginstitutet för cancerforskning (author)
- Lomnytska, MartaUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)marlo829 (author)
- Heldin, Carl-HenrikUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)carlheld (author)
- Volodko, Natalya (author)
- Souchelnytskyi, SerhiyKarolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)sergsouc (author)
- Uppsala universitetLudwiginstitutet för cancerforskning (creator_code:org_t)
Related titles
- In:Oncogene: Springer Science and Business Media LLC24:14, s. 2289-22970950-92321476-5594
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