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The 6HMM protein is a human poly (ADP-ribose) glycohydrolase. It is an enzyme that will catalyze the hydrolysis of glycosides, here more specifically it will produce a free ADP-ribose. This protein is only present when the DNA is damaged. It influences the damaged chromatin through a derepression on a gene promoter. Consequently this protein is quite interesting for biotechnical applications. Indeed, developing proteins who repair DNA damage is a meaningful goal in research. Moreover, this protein is found in humans, so understanding its structure could have an impact on humans.

Structure

Structural highlights

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Links of PARG with other ligands

Function

The protein is a complex composed of the poly (ADP-ribose) glycohydrolase (PARG) and anthraquinone PDD00013907. The post-translational modifications of the PAR protein (poly ADP-ribose) are important for DNA stability. PDD00013907 is an anthraquinone which is a polycyclic aromatic hydrocarbon usually used in biopesticides as a pest repellant. Here it is considered as a free ligand (of identification number on PDB: 7JB) that can bind to the PARG creating the protein complex 6HMM.

Post-translational modifications to stabilize DNA

There are several possible post-translational modifications to stabilize DNA. Most commonly they would be phosphorylation, acetylation or methylation ^[3]. Another post-translational modification concerning the 6HMM protein is made on the PAR protein. The PARG is used for the hydrolyzation of specific ribose-ribose bonds present in PAR which leads to the degradation of PAR ^[4].

The mechanism

As said previously, poly(ADP-ribosylation) is an important post-translational modification for DNA repair. The mechanism behind this repair relies on several factors. At first, the Poly (ADP-ribose) polymerase (PARP), more specifically the subtype PARP1, will recognize and will bind to the single-strand break. It will then autophosphorylate due to NAD+ and form PAR chains. These will then recruit other repair proteins to the site. The role of PARG is to degrade the ADP-ribosepolymers on PARP through a catalytic cycle ^[5].

Diseases and Relevance