ENDOG

Description

The ENDOG (endonuclease G) is a protein-coding gene located on chromosome 9.

Endonuclease G, mitochondrial is an enzyme encoded by the ENDOG gene in humans. Its primary function is in caspase-independent apoptosis, where it degrades DNA during translocation from the mitochondrion to the nucleus under oxidative stress. This role implicates EndoG in cancer, aging, and neurodegenerative diseases such as Parkinson's disease (PD). Regulating its expression levels has therapeutic potential for these conditions. EndoG is a member of the DNA/RNA non-specific ββα-Me-finger nuclease family and has a unique affinity for poly(dG).poly(dC) sequences in double-stranded DNA. Synthesized as an inactive 33-kDa precursor, it is activated by proteolytic cleavage, generating a mature 28-kDa enzyme that translocates to the mitochondrial intermembrane space and forms an active homodimer. The H-N-N motif (His-141, Asn-163, Asn-172) is crucial for its catalytic function and substrate specificity, with His-141 being essential for magnesium coordination. Although Asn-251 and Glu-271 appear catalytic and involved in magnesium binding, their interactions are unclear due to their distance from the H-N-N motif. EndoG, a nuclear-encoded endonuclease, is localized in the mitochondrial intermembrane space and is widely distributed among animals. It cleaves DNA at GC tracts.

Endonuclease G (EndoG) is an enzyme that preferentially cleaves double-stranded DNA containing 5-hydroxymethylcytosine (5hmC) modifications. While 5hmC does not enhance binding, it increases cleavage efficiency and determines the specific site of cleavage. EndoG displays a significantly higher affinity for four-stranded Holliday junctions compared to duplex and single-stranded DNAs. It promotes conservative recombination in the presence of 5hmC-modified DNA. Furthermore, EndoG plays a role in autophagy by suppressing mTOR through its phosphorylation-mediated interaction with YWHAG and its endonuclease activity-induced DNA damage response. GSK3-beta phosphorylation of EndoG enhances its interaction with YWHAG, leading to the release of TSC2 and PIK3C3 from YWHAG, thereby suppressing the mTOR pathway and initiating autophagy. In response to oxidative and nitrosative stress, EndoG promotes the cleavage of mitochondrial DNA (mtDNA), triggering compensatory mtDNA replication.

ENDOG is also known as -.

Associated Diseases

WES Whole Exome Sequencing