Chromatin lysine acylation: On the path to chromatin homeostasis and genome integrity

The fundamental role of cells in safeguarding the genome's integrity against DNA double‐strand breaks (DSBs) is crucial for maintaining chromatin homeostasis and the overall genomic stability. Aberrant responses to DNA damage, known as DNA damage responses (DDRs), can result in genomic instability and contribute significantly to tumorigenesis. Unraveling the intricate mechanisms underlying DDRs following severe damage holds the key to identify therapeutic targets for cancer. Chromatin lysine acylation, encompassing diverse modifications such as acetylation, lactylation, crotonylation, succinylation, malonylation, glutarylation, propionylation, and butyrylation, has been extensively studied in the context of DDRs and chromatin homeostasis. Here, we delve into the modifying enzymes and the pivotal roles of lysine acylation and their crosstalk in maintaining chromatin homeostasis and genome integrity in response to DDRs. Moreover, we offer a comprehensive perspective and overview of the latest insights, driven primarily by chromatin acylation modification and associated regulators. An overview of lysine acylation modification connections to metabolic process. The energy resources, such as glucose, fatty acids, and amino acids, are metabolized by cells to produce different types of acyl‐CoA, which function as donors for chromatin lysine acylation modification in response to DNA‐damaging stress.