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

Author

Listed:
  • Swarnalatha Manickavinayaham

    (The University of Texas MD Anderson Cancer Center)

  • Renier Vélez-Cruz

    (The University of Texas MD Anderson Cancer Center
    Midwestern University, Chicago College of Osteopathic Medicine)

  • Anup K. Biswas

    (The University of Texas MD Anderson Cancer Center
    Columbia University)

  • 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)

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.

Suggested Citation

  • Swarnalatha Manickavinayaham & Renier Vélez-Cruz & Anup K. Biswas & Ella Bedford & Brianna J. Klein & Tatiana G. Kutateladze & Bin Liu & Mark T. Bedford & David G. Johnson, 2019. "E2F1 acetylation directs p300/CBP-mediated histone acetylation at DNA double-strand breaks to facilitate repair," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12861-8
    DOI: 10.1038/s41467-019-12861-8
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    Cited by:

    1. Sree Deepthi Muthukrishnan & Riki Kawaguchi & Pooja Nair & Rachna Prasad & Yue Qin & Maverick Johnson & Qing Wang & Nathan VanderVeer-Harris & Amy Pham & Alvaro G. Alvarado & Michael C. Condro & Fuyin, 2022. "P300 promotes tumor recurrence by regulating radiation-induced conversion of glioma stem cells to vascular-like cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Manish Kumar & David Molkentine & Jessica Molkentine & Kathleen Bridges & Tongxin Xie & Liangpeng Yang & Andrew Hefner & Meng Gao & Reshub Bahri & Annika Dhawan & Mitchell J. Frederick & Sahil Seth & , 2021. "Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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