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Published on: January 31, 2018
Chromatin Ubiquitination Guides DNA Double Strand Break Signaling and Repair
Ksenia G Kolobynina1, Alexander Rapp1, M Cristina Cardoso1
1Department of Biology, Cell Biology and Epigenetics, Technical University of Darmstadt, Darmstadt, Germany.
Abstract:
Chromatin is the context for all DNA-based molecular processes taking place in the cell nucleus. The initial chromatin structure at the site of the DNA damage determines both, lesion generation and subsequent activation of the DNA damage response (DDR) pathway. In turn, proceeding DDR changes the chromatin at the damaged site and across large fractions of the genome. Ubiquitination, besides phosphorylation and methylation, was characterized as an important chromatin post-translational modification (PTM) occurring at the DNA damage site and persisting during the duration of the DDR. Ubiquitination appears to function as a highly versatile "signal-response" network involving several types of players performing various functions. Here we discuss how ubiquitin modifiers fine-tune the DNA damage recognition and response and how the interaction with other chromatin modifications ensures cell survival.
Insights
Chromatin structure influences DNA damage and the DNA damage response (DDR). Ubiquitination, a key post-translational modification, fine-tunes DDR signaling and interacts with other modifications to ensure cell survival.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Chromatin serves as the nuclear context for all DNA-related processes.
- Initial chromatin structure at DNA damage sites influences lesion formation and DNA damage response (DDR) pathway activation.
- The DDR pathway dynamically alters chromatin structure at damage sites and genome-wide.
Purpose of the Study:
- To explore the role of ubiquitination in DNA damage recognition and response.
- To discuss how ubiquitin modifiers interact with other chromatin modifications.
- To understand how these interactions contribute to cell survival.
Main Methods:
- Review of existing literature on chromatin modifications and DNA damage response.
- Analysis of the mechanisms by which ubiquitination impacts DDR pathways.
- Examination of the interplay between ubiquitination and other post-translational modifications (PTMs) like phosphorylation and methylation.
Main Results:
- Ubiquitination is a crucial post-translational modification at DNA damage sites, persisting throughout the DDR.
- Ubiquitin modifiers act as a versatile signal-response network, regulating DNA damage recognition and repair.
- Interactions between ubiquitination and other chromatin modifications are essential for maintaining genomic stability and cell survival.
Conclusions:
- Ubiquitination plays a pivotal role in modulating the cellular response to DNA damage.
- The integration of ubiquitination with other chromatin modifications is critical for effective DNA repair and cell survival.
- Understanding these complex regulatory networks offers insights into potential therapeutic strategies for diseases involving DNA damage.
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