Authors

L Visochek, Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University
G Grigoryan, Department of Neurobiology, Weizmann Institute of Science; Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig
A Kalal, Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University; Department of Physiology and Pharmacology, Tel-Aviv University
H Milshtein-Parush, Department of Physiology and Pharmacology, Tel-Aviv University; Sagol School of Neuroscience, Tel-Aviv University
N Gazit, Department of Physiology and Pharmacology, Tel-Aviv University; Sagol School of Neuroscience, Tel-Aviv University
I Slutsky, Department of Physiology and Pharmacology, Tel-Aviv University; Sagol School of Neuroscience, Tel-Aviv University
A Yeheskel, Bioinformatics Unit, George S. Wise Faculty of Life Sciences, Tel-Aviv University
A Shainberg, Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University
A Castiel, Cancer Research Center, Sheba Medical Center
R Seger, Department of Biological Regulation, Weizmann Institute of Science
Marie-France Langelier, Department of Biochemistry and Molecular Biology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
F Dantzer, Biotechnology and Cell Signaling, UMR7242, Ecole Superieure de Biotechnologie Strasbourg
Pascal Jabbour MD, Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityFollow
M Segal, Department of Neurobiology, Weizmann Institute of Science
M Cohen-Armon, Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University; Department of Physiology and Pharmacology, Tel-Aviv University; Sagol School of Neuroscience, Tel-Aviv University

Document Type

Article

Publication Date

4-26-2016

Comments

This article has been peer reviewed. It was published in: Scientific Reports.

Volume 6, 28 April 2016, Article number 24950.

The published version is available at DOI: 10.1038/srep24950

Copyright © 2016, The Authors

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Abstract

Unexpectedly, a post-translational modification of DNA-binding proteins, initiating the cell response to single-strand DNA damage, was also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk synergism, which may underlie this phenomenon. A stimulation induced PARP1 binding to phosphorylated Erk2 in the chromatin of cerebral neurons caused Erk-induced PARP1 activation, rendering transcription factors and promoters of immediate early genes (IEG) accessible to PARP1-bound phosphorylated Erk2. Thus, Erk-induced PARP1 activation mediated IEG expression implicated in long-term memory. PARP1 inhibition, silencing, or genetic deletion abrogated stimulation-induced Erk-recruitment to IEG promoters, gene expression and LTP generation in hippocampal CA3-CA1-connections. Moreover, a predominant binding of PARP1 to single-strand DNA breaks, occluding its Erk binding sites, suppressed IEG expression and prevented the generation of LTP. These findings outline a PARP1-dependent mechanism required for LTP generation, which may be implicated in long-term memory acquisition and in its deterioration in senescence.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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