Journal
BIOMOLECULES
Volume 12, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/biom12101428
Keywords
lysine crotonylation; DNA damage response (DDR); DNA double-strand break (DSB); DNA replication stress response
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Funding
- National Natural Science Foundation of China [31971221, 31370841]
- Beijing Natural Science Foundation [5182003]
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Lysine crotonylation is a reversible protein posttranslational modification that plays a crucial role in maintaining genome stability and responding to genotoxic stresses. It connects cellular metabolism with gene regulation and is involved in various cellular processes, including transcriptional repression induced by double-strand breaks, DNA repair, and the response to DNA replication stress.
The DNA damage response (DDR) system plays an important role in maintaining genome stability and preventing related diseases. The DDR network comprises many proteins and posttranslational modifications (PTMs) to proteins, which work in a coordinated manner to counteract various genotoxic stresses. Lysine crotonylation (Kcr) is a newly identified PTM occurring in both core histone and non-histone proteins in various organisms. This novel PTM is classified as a reversible acylation modification, which is regulated by a variety of acylases and deacylases and the intracellular crotonyl-CoA substrate concentration. Recent studies suggest that Kcr links cellular metabolism with gene regulation and is involved in numerous cellular processes. In this review, we summarize the regulatory mechanisms of Kcr and its functions in DDR, including its involvement in double-strand break (DSB)-induced transcriptional repression, DSB repair, and the DNA replication stress response.
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