The Hidden Side of DNA Damage: How 8-oxoGua and OGG1 Impact Cancer

When your body's cells produce energy, they also create byproducts called reactive oxygen species (ROS). These can damage DNA in various ways, one of the most common being the oxidation of guanine, a building block of DNA. This oxidized form is known as 8-oxoguanine (8-oxoGua). If not fixed, 8-oxoGua can pair with the wrong base during DNA replication, leading to a mutation. This is where an enzyme called 8-oxoguanine DNA glycosylase 1 (OGG1) steps in. OGG1 acts like a DNA repair worker, spotting 8-oxoGua and starting a process called base excision repair (BER) to remove the damage. For a long time, scientists have linked the buildup of 8-oxoGua and the malfunction of OGG1 to mutations that can cause aging-related diseases and even cancer. However, direct proof was scarce. Recently, researchers found that the oxidation of guanine isn't random; it tends to happen in specific parts of the genome called regulatory regions. This means 8-oxoGua isn't just a damage to be fixed, but also a kind of epigenetic modification, like a tag that can change how genes are expressed. OGG1 can read this tag and, by doing so, can alter the shape of DNA and how it's packed in the cell, affecting the expression of genes involved in processes like inflammation, cell growth, differentiation, and cell death. So, 8-oxoGua might contribute to cancer development and progression not only through causing mutations but also by changing how certain genes behave. This adds a new layer to understanding how DNA damage can influence cancer.