DNAsträngbrott

DNAsträngbrott, or DNA strand breaks, are physical discontinuities in the phosphodiester backbone of a DNA molecule. These breaks can occur in either one strand (single-strand breaks or SSBs) or both strands (double-strand breaks or DSBs). SSBs are generally less severe and can be repaired by cellular mechanisms, while DSBs are considered more dangerous as they can lead to chromosomal rearrangements and are more difficult for the cell to repair accurately.

These breaks can arise from a variety of sources. Endogenous factors include errors during DNA replication, the action of reactive oxygen species (ROS) generated during normal metabolic processes, and enzymatic activities within the cell. Exogenous factors include exposure to ionizing radiation (like X-rays or gamma rays), certain chemical agents (such as topoisomerases inhibitors or intercalating agents), and UV radiation, which primarily causes SSBs or base damage that can lead to strand breaks.

The cell has evolved sophisticated DNA repair pathways to deal with strand breaks. For SSBs, base excision repair (BER) and nucleotide excision repair (NER) are key pathways. For DSBs, two major pathways exist: non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ is a rapid but error-prone mechanism that directly ligates broken ends, while HR is a more accurate pathway that uses a homologous template (usually the sister chromatid) to repair the break. If these repair mechanisms fail or are overwhelmed, DNA strand breaks can lead to mutations, genomic instability, and ultimately cell death or cancer.