Nucleotide Excision Repair and Cancer

Cancer ranks as one of the most frequent causes of death worldwide and in Western society it is competing with cardiovascular disease as the number one killer. This high frequency in Western countries can be attributed to lifestyle and environmental factors, only 5-10% of all cancers are directly due to heredity. Common environmental factors leading to cancer include: tobacco (25-30%), diet and obesity (30-35%), infections (15-20%), radiation, lack of physical activity and environmental pollutants or chemicals (Anand et al.,2008). Exposure to these environmental factors cause or enhance abnormalities in the genetic material of cells (Kinzler KW et al.,2002). These changes in the DNA or hereditary predisposition can result in respectively uncontrolled cell growth, invasion and metastasis. Cancer cells can damage tissue and disturb homeostasis leading to dysfunctions in the body that can eventually lead to death. Under normal conditions cell growth is under strict conditions and control. Hereditary dysfunctions or introduced DNA damage in tumor suppressor genes, oncogenes or DNA repair genes can create an imbalance that may lead to cancer development. DNA repair and cell cycle arrest pathways are essential cellular mechanisms to prevent or repair substantial DNA damage which, if left unattended, can cause diseases. Here, one of the most important and versatile DNA repair pathways, the Nucleotide Excision Repair (NER) pathway, will be discussed in relation to DNA damage accumulation and carcinogenesis together with its mechanistic mode of action.