Back to Search
Start Over
E2F1 acetylation directs p300/CBP-mediated histone acetylation at DNA double-strand breaks to facilitate repair
- Source :
- Nature Communications, Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019)
- Publication Year :
- 2019
-
Abstract
- E2F1 and retinoblastoma (RB) tumor-suppressor protein not only regulate the periodic expression of genes important for cell proliferation, but also localize to DNA double-strand breaks (DSBs) to promote repair. E2F1 is acetylated in response to DNA damage but the role this plays in DNA repair is unknown. Here we demonstrate that E2F1 acetylation creates a binding motif for the bromodomains of the p300/KAT3B and CBP/KAT3A acetyltransferases and that this interaction is required for the recruitment of p300 and CBP to DSBs and the induction of histone acetylation at sites of damage. A knock-in mutation that blocks E2F1 acetylation abolishes the recruitment of p300 and CBP to DSBs and also the accumulation of other chromatin modifying activities and repair factors, including Tip60, BRG1 and NBS1, and renders mice hypersensitive to ionizing radiation (IR). These findings reveal an important role for E2F1 acetylation in orchestrating the remodeling of chromatin structure at DSBs to facilitate repair.<br />E2F1, which localises to DNA double-strand breaks (DSBs) to promote repair, is acetylated in response to DNA damage but the role this plays in DNA repair is unknown. Here the authors show that E2F1 acetylation creates a binding motif for the bromodomains of the p300/KAT3B and CBP/KAT3A acetyltransferases, which is required for recruitment of p300 and CBP to DSBs, to facilate repair.
- Subjects :
- 0301 basic medicine
DNA Repair
Molecular biology
General Physics and Astronomy
Cell Cycle Proteins
Histones
Mice
0302 clinical medicine
Radiation, Ionizing
E2F1
DNA Breaks, Double-Stranded
p300-CBP Transcription Factors
Gene Knock-In Techniques
lcsh:Science
Histone Acetyltransferases
Cancer
Multidisciplinary
biology
Chemistry
Nuclear Proteins
Acetylation
CREB-Binding Protein
Chromatin
Cell biology
DNA-Binding Proteins
Histone
030220 oncology & carcinogenesis
biological phenomena, cell phenomena, and immunity
endocrine system
DNA repair
DNA damage
Science
General Biochemistry, Genetics and Molecular Biology
Lysine Acetyltransferase 5
Article
03 medical and health sciences
Genetics
Animals
Protein Interaction Domains and Motifs
DNA Helicases
General Chemistry
Bromodomain
030104 developmental biology
biology.protein
Trans-Activators
lcsh:Q
E1A-Associated p300 Protein
E2F1 Transcription Factor
Transcription Factors
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....25200987af4e5fd014c0d035f6129b4a