TY  - JOUR
A1  - Volcic, Meta
A1  - Karl, Sabine
A1  - Baumann, Bernd
A1  - Salles, Daniela
A1  - Daniel, Peter
A1  - Fulda, Simone
A1  - Wiesmüller, Lisa
T1  - NF-κB regulates DNA double-strand break repair in conjunction with BRCA1-CtIP complexes
T2  - Nucleic acids research
N2  - NF-κB is involved in immune responses, inflammation, oncogenesis, cell proliferation and apoptosis. Even though NF-κB can be activated by DNA damage via Ataxia telangiectasia-mutated (ATM) signalling, little was known about an involvement in DNA repair. In this work, we dissected distinct DNA double-strand break (DSB) repair mechanisms revealing a stimulatory role of NF-κB in homologous recombination (HR). This effect was independent of chromatin context, cell cycle distribution or cross-talk with p53. It was not mediated by the transcriptional NF-κB targets Bcl2, BAX or Ku70, known for their dual roles in apoptosis and DSB repair. A contribution by Bcl-xL was abrogated when caspases were inhibited. Notably, HR induction by NF-κB required the targets ATM and BRCA2. Additionally, we provide evidence that NF-κB interacts with CtIP-BRCA1 complexes and promotes BRCA1 stabilization, and thereby contributes to HR induction. Immunofluorescence analysis revealed accelerated formation of replication protein A (RPA) and Rad51 foci upon NF-κB activation indicating HR stimulation through DSB resection by the interacting CtIP-BRCA1 complex and Rad51 filament formation. Taken together, these results define multiple NF-κB-dependent mechanisms regulating HR induction, and thereby providing a novel intriguing explanation for both NF-κB-mediated resistance to chemo- and radiotherapies as well as for the sensitization by pharmaceutical intervention of NF-κB activation
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24840
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-248407
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245919/
SN  - 1362-4962
SN  - 0305-1048
N1  - (c) The Author(s) 2011. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 40
IS  - 1
SP  - 181
EP  - 195
PB  - Oxford Univ. Press
CY  - Oxford
ER  -