Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function

Autor: 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, Mohamed Abdelhakiem, Beth M. Beadle, Faye Johnson, Jing Wang, Li Shen, Timothy Heffernan, Aakash Sheth, Robert L. Ferris, Jeffrey N. Myers, Curtis R. Pickering, Heath D. Skinner
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-021-26570-8
Popis: Mutations in histone acetyltransferases (HATs) CREBBP and EP300 are generally thought to lead to decreased function or absence of protein product. Here the authors describe a gain of function of several CREBBP mutations leading to baseline hyper-acetylation, increased homologous recombination and potential synergy between radiation and HAT inhibition in CREBBP/EP300 mutant tumors.
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