E2F1 acetylation directs p300/CBP-mediated histone acetylation at DNA double-strand breaks to facilitate repair

Swarnalatha Manickavinayaham, Renier Vélez-Cruz, Anup K. Biswas, Ella Bedford, Brianna J. Klein, Tatiana G. Kutateladze, Bin Liu, Mark T. Bedford and David G. Johnson ()
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Swarnalatha Manickavinayaham: The University of Texas MD Anderson Cancer Center
Renier Vélez-Cruz: The University of Texas MD Anderson Cancer Center
Anup K. Biswas: The University of Texas MD Anderson Cancer Center
Ella Bedford: The University of Texas MD Anderson Cancer Center
Brianna J. Klein: University of Colorado School of Medicine
Tatiana G. Kutateladze: University of Colorado School of Medicine
Bin Liu: The University of Texas MD Anderson Cancer Center
Mark T. Bedford: The University of Texas MD Anderson Cancer Center
David G. Johnson: The University of Texas MD Anderson Cancer Center

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12861-8

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