Figure 8.
Model for cellular processing of UV-induced DNA damage. UV radiation induces mainly pyrimidine cyclobutane dimers and 6-4 photoproducts. The majority of these are repaired by nucleotide excision repair (NER), which involves recognition of the site of damage by XPA with the assistance of RPA and the recruitment of additional repair proteins that incise the DNA on either side of the damage, release a single-stranded oligonucleotide containing the damage and fill in the resulting gap. If cells are in S phase and DNA replication occurs before all the damage is repaired, the DNA replication fork may encounter sites of damage. One of several specialized DNA polymerases may facilitate replication past the damage. If replication becomes stalled at sites of DNA damage, mechanisms of postreplication repair (PRR) are activated. This activation appears to involve the ATM kinase, which phosphorylates RPA and NBS1. The MRE11/RAD50/NBS1 complex may participate in processing the incompletely replicated DNA, facilitating recombinational repair.