DNADamageResponse

DNADamageResponse is the set of cellular processes activated in response to DNA damage in order to preserve genome integrity. It encompasses damage sensing, signal transduction, and effector responses that coordinate cell cycle control, DNA repair, and, when necessary, programmed cell fate decisions.

Core components of the DNADamageResponse include sensor proteins that recognize lesions and recruit kinase signaling cascades. Key sensors are protein kinases such as ATM, ATR, and DNA-PK, which phosphorylate downstream transducers like CHK1 and CHK2. These transducers relay signals to effectors such as p53, BRCA1/2, and various DNA repair proteins, leading to outcomes that depend on the type and context of damage. A hallmark of the response is the modification of chromatin, including γ-H2AX formation at damage sites, which helps recruit repair machinery.

The DNADamageResponse regulates cell cycle checkpoints, enabling time for repair before replication or division. It also governs repair pathway choice, with mechanisms including base excision repair, nucleotide excision repair, mismatch repair, homologous recombination, and non-homologous end joining. When damage is irreparable, the response can induce apoptosis or cellular senescence to prevent propagation of mutations.

In research and medicine, the DNADamageResponse is studied to understand cancer, aging, and responses to genotoxic therapies. It is a broad and evolving concept that intersects molecular signaling, DNA repair, chromatin biology, and cell fate regulation.