Endog

What is ENDOG protein?

ENDOG (endonuclease G) gene is a protein coding gene which situated on the long arm of chromosome 9 at locus 9q34. The protein encoded by this gene is a nuclear encoded endonuclease that is localized in the mitochondrion. The encoded protein is widely distributed among animals and cleaves DNA at GC tracts. This protein is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA. The ENDOG protein is consisted of 297 amino acids and its molecular mass is approximately 32.6 kDa.

What is the function of ENDOG protein?

ENDOG is a ribonuclease that plays an important role in cells, especially in the recognition and repair of DNA damage. ENDOG is able to specifically recognize and cut single-strand breaks in double-stranded DNA, triggering the cell's DNA damage response mechanism. This function is essential for maintaining the stability of the genome and preventing the accumulation of mutations. In addition to its role in DNA repair, ENDOG is also involved in the regulation of cell cycle progression, apoptosis, and immune response.

ENDOG Related Signaling Pathway

Signaling pathways in which ENDOG proteins may be involved include: Mitochondrial apoptosis pathway: ENDOG protein can be released along with mPT in mitochondria, leading to mitochondrial apoptosis;

DNA damage repair pathway: ENDOG protein is involved in the repair and degradation of mitochondrial DNA and maintains the stability of DNA in cells, thus affecting the DNA damage repair pathway. In addition, ENDOG is involved in cell cycle regulation by influencing the activity of checkpoint kinases such as Chk1 and Chk2.

Fig1. The propagation phase of acetaminophen-induced cell death. (Hartmut Jaeschke, 2021)

ENDOG Related Diseases

Mutations in the ENDOG gene have been associated with several genetic disorders, such as Fanconi anemia, Bloom syndrome and Xeroderma pigmentosum. These diseases are mainly due to defects in DNA repair mechanisms leading to genomic instability, which leads to a variety of cancers and genetic diseases. It can also cause diseases of the immune system or nervous system.

Bioapplications of ENDOG

Although the application of ENDOG protein is mainly in the field of scientific research, its application in the study of apoptosis and mitochondrial function has shown its potential biomedical value. ENDOG may have potential applications in diseases such as tumors, autoimmune diseases, and neurodegenerative diseases.

Case study 1: Sumedha Dahal, 2022

Having its genome makes the mitochondrion a unique and semiautonomous organelle within cells. Mapping the deletion junctions suggests that the breakpoints are generally seen at hotspots. '9 bp deletion' (8271-8281). While it is associated with several diseases like myopathy, dystonia, and hepatocellular carcinoma, it has also been used as an evolutionary marker. However, the mechanism responsible for its fragility is unclear.

In the current study, the researchers show that Endonuclease G, a mitochondrial nuclease responsible for nonspecific cleavage of nuclear DNA during apoptosis, can induce breaks at sequences associated with '9 bp deletion' when it is present on a plasmid or in the mitochondrial genome. Through a series of in vitro and intracellular studies, they show that Endonuclease G binds to G-quadruplex structures formed at the hotspot and induces DNA breaks. Therefore, they uncover a new role for Endonuclease G in generating mtDNA deletions, which depends on the formation of G4 DNA within the mitochondrial genome.

Fig1. In vitro nicking assay using purified Endonuclease G on wild type and mutant plasmids containing mitochondrial Region I (pDI1 and pDI2).

Fig2. Localization of Endonuclease G in mitochondria in different cell lines.

Case study 2: Tung Chao, 2021

Genotoxic insult causes nuclear and mitochondrial DNA damages with macroautophagy/autophagy induction. The role of mitochondrial DNA (mtDNA) damage in the requirement of autophagy for nuclear DNA (nDNA) stability is unclear. Using site-specific DNA damage approaches, we show that specific nDNA damage alone does not require autophagy for repair unless in the presence of mtDNA damage.

The researchers provide evidence that after IR exposure-induced mtDNA and nDNA damages, autophagy suppression causes non-apoptotic mitochondrial permeability, by which mitochondrial ENDOG (endonuclease G) is released. Furthermore, blocking lysosome function is sufficient to increase the amount of mtDNA leakage to the cytosol, accompanied by ENDOG-free mitochondrial puncta formation with concurrent ENDOG nuclear accumulation. Finally, the researchers showed that HBx, a hepatitis B viral protein capable of suppressing autophagy, also causes mitochondrial permeability-dependent ENDOG mis-localization in nuclei and is linked to hepatitis B virus (HBV)-mediated hepatocellular carcinoma development.

Fig3. The role of ENDOG in nDNA damage. Cells infected with lentivirus of the shRNA of ENDOG for γH2AX IF staining at the time recovery from IR.

Fig4. Effect of TET2 and ENDOG overexpression on nDNA damage. Cells were transfected with GFP or TET2-GFP in combination with ENDOG-GFP plasmids.

Endog has several biochemical functions, for example, deoxyribonuclease activity,endonuclease activity,metal ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Endog itself. We selected most functions Endog had, and list some proteins which have the same functions with Endog. You can find most of the proteins on our site.

Endog has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Endog here. Most of them are supplied by our site. Hope this information will be useful for your research of Endog.

DNAJA4;q96be0_human