Double-Strand Break Repair and Homologous Recombination in Mammalian Cells

A paradigm shift has occurred over the last few years in the understanding of homologous recombination. It has long been known that DNA double-strand breaks (DSBs) in yeast are potent inducers of homologous recombination and that homologous recombination is the major pathway in yeast to repair DSBs (Chapter 16, Vol. 1). Compared with nonhomologous repair, homologous recombination has generally been considered to be inconsequential as a DSB repair pathway in mammalian cells. However, homologous repair can precisely restore the damaged DNA to its original sequence, suggesting that it should be a preferred pathway for repair, at least under some circumstances. Recently, direct examination of repair products in mammalian cells has demonstrated the importance of homologous recombination during the repair of DSBs. Supporting this conclusion has been the identification of DNA repair defects in mutant cell lines and the construction of mouse knockouts of genes implicated in homologous recombination. This chapter discusses basic parameters of DSB repair by homologous recombination in mammalian cells and emerging evidence for the involvement of various proteins in the repair process.