Deoxyribonuclease Functionality in Apoptotic Processes

Apoptosis is a tightly regulated form of programmed cell death that shapes tissue development, maintains cellular homeostasis and prevents the release of harmful intracellular contents. Central to this process is the systematic degradation of chromosomal DNA, a role fulfilled by specialised deoxyribonucleases. Following activation of upstream proteases, caspase-activated DNase (CAD) and various Ca2+-dependent endonucleases translocate to the nucleus, where they cleave chromatin into oligonucleosomal fragments. This internucleosomal DNA fragmentation not only ensures orderly nuclear condensation but also flags dying cells for rapid phagocytic clearance, thus averting inflammation and autoimmunity. Additional DNase family members, such as DNase I and DNAS1L3, contribute cooperatively to chromatin dismantling and the removal of extracellular DNA. Dysregulated DNase activity is implicated in autoimmune conditions, cancer progression and degenerative diseases, while exogenous DNase administration has begun to demonstrate therapeutic benefit in preclinical inflammatory models. Advances in our understanding of DNase regulation, substrate specificity and inter-enzyme cooperation are driving the design of novel modulators with potential applications in immunotherapy, tissue repair and the treatment of DNase-related pathologies.

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Deoxyribonuclease Functionality in Apoptotic Processes publication trend

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Technical terms

Apoptosis: Programmed cell death characterised by energy-dependent biochemical events leading to cell shrinkage, chromatin condensation and DNA fragmentation.

Deoxyribonuclease (DNase): Enzyme class that hydrolyses DNA phosphodiester bonds, mediating chromatin cleavage during apoptosis and extracellular DNA clearance.

Caspase-activated DNase (CAD): Principal apoptotic endonuclease activated upon cleavage of its inhibitor ICAD by executioner caspases, responsible for internucleosomal DNA fragmentation.

Internucleosomal DNA Fragmentation (INDF): The orderly cleavage of DNA at linker regions between nucleosomes, producing a characteristic ladder pattern on electrophoresis.

Inhibitor of CAD (ICAD): Chaperone protein that binds and inactivates CAD under non-apoptotic conditions; its proteolytic removal permits CAD activation.

References

1. Apoptotic DNA Fragmentation May Be a Cooperative Activity between Caspase-activated Deoxyribonuclease and the Poly(ADP-ribose) Polymerase-regulated DNAS1L3, an Endoplasmic Reticulum-localized Endonuclease That Translocates to the Nucleus during Apoptosis*. Journal of Biological Chemistry (2012).
2. Auxin-induced Rapid Degradation of Inhibitor of Caspase-activated DNase (ICAD) Induces Apoptotic DNA Fragmentation, Caspase Activation, and Cell Death A Cell Suicide Module*. Journal of Biological Chemistry (2014).
3. DNase I Induces Other Endonucleases in Kidney Tubular Epithelial Cells by Its DNA-Degrading Activity. International Journal of Molecular Sciences (2020).