DNA Structure, Damage, and Repair

To maintain the stability of their genome, cells have developed multi-component damage detection and repair systems to address single strand damage as well as double strand breaks. Examples of single strand damage repair systems include nucleotide excision repair (NER), base excision repair (BER), and mismatch repair. Double stranded breaks are addressed using one of the double strand break repair mechanisms (DSBs). These mechanisms are known as non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination.

At sites of DNA damage histone H2A.X is recruited to the site and becomes phosphorylated at serine 139. This histone also known as gamma H2A.X serves as a binding site for MDC1 which helps recruited DNA repair proteins

In dividing cells, cell cycle check points are activated in response to DNA damage. These check points result in a pause to cell division and allow the repair mechanisms to function. If these detection and repair systems fail, cells can become senescent, apoptotic, or undergo autophagy to prevent the cells from proliferating. If these ‘back-up systems’ fail these aberrant cells survive and continue to divide and result in the development of diseases such as cancer. In some cases the repair mechanisms are unable to detect the error. When errors in DNA methylation occur such as the spontaneous deamination of 5-methylcytosine, the loss of the amine group yields a thymine base. This change is not detected as an unnatural base. The resulting substitution is retained in DNA replication, creating a C→T point mutation.