Repair Single stranded breaks (SSBs) can severely threaten genetic stability and cell survival if not quickly and properly repaired, so cells have developed fast and efficient SSB repair (SSBR) mechanisms. While global SSBR systems extract SSBs throughout the genome and during interphase, S-phase specific SSBR processes work together with homologous recombination at the replication forks. Double Stranded Break Repair Double stranded breaks (DSB) are a threat to all organisms as they can cause cell death and cancer. They can be caused exogenously as a result of radiation and endogenously from errors in replication or encounters with DNA lesions by the replication fork. DSB repair occurs through a variety of different pathways and mechanisms in order to correctly repair these errors. Nucleotide Excision and Mismatch Repair Nucleotide excision repair is one of the main mechanisms used to remove bulky adducts from DNA lesions caused by chemotherapy drugs, environmental mutagens, and most importantly UV radiation. This mechanism functions by releasing a short damage containing oligonucleotide from the DNA site, and then that gap is filled in and repaired by NER. NER recognizes a variety of structurally unrelated DNA lesions due to the flexibility of the mechanism itself, as NER is highly sensitive to changes in the DNA helical structure. Bulky adducts seem to trigger NER. The XPC-RAD23-CETN2 heterotrimer involved with NER has a critical role in DNA lesion recognition. In addition to other general lesions in the genome, UV damaged DNA binding protein complex (UV-DDB) also has an important role in both recognition and repair of UV-induced DNA photolesions. Mismatch repair (MMR) mechanisms within the cell correct base mispairs that occur during replication using a variety of pathways. It has a high affinity for targeting DNA lesions with specificity, as alternations in base pair stacking that occur at DNA lesion sites affect the helical structure. This is likely one of many signals that triggers MMR. References Molecular biology