Binding of double-strand breaks in DNA by human Rad52 protein

Double-strand breaks (DSBs) in DNA are caused by ionizing radiation. These chromosomal breaks can kill the cell unless repaired efficiently, and ineff icient or inappropriate repair can lead to mutation, gene translocation and cancer(1), Two proteins that participate in the repair of DSBs are Rad52 a nd Ku: in lower eukaryotes such as yeast, DSBs are repaired by Rad52-depend ent homologous recombination, whereas vertebrates repair DSBs primarily by Ku-dependent non-homologous end-joining(2). The contribution of homologous recombination to vertebrate DSB repair, however, is important(3,4). Biochem ical studies indicate that Ku binds to DNA ends and facilitates end-joining (5). Here we show that human Rad52, like Ku, binds directly to DSBs, protec ts them from exonuclease attack and facilitates end-to-end interactions. A model for repair is proposed in which either Ku or Rad52 binds the DSB. Ku directs DSBs into the non-homologous end-joining repair pathway, whereas Ra d52 initiates repair by homologous recombination. Ku and Rad52, therefore, direct entry into alternative pathways for the repair of DNA breaks.