The need for Nbs1

Eukaryotic cells have developed two independent pathways to repair double-strand breaks (DSB) in their DNA: non-homologous end-joining (NHEJ) and homologous recombination. A complex containing Mre11, Rad50 and Nbs1 proteins has been implicated in DSB repair, but its exact function is unclear. In the November 7 Nature, Tauchi et al. characterized the role of the Mre11-Rad50-Nbs1 complex in vertebrate cells by creating Nbs1 knockout cells (Nature 2002, 420:93-98). The recombinogenic chicken B-cell line DT40 was used to generate cells lacking a functional Nbs1 allele. The knockout cell line was hypersensitive to ionizing radiation and displayed abnormal S-phase checkpoint behavior. These cells did not exhibit a profound end-joining defect; but loss of Nbs1 resulted in reduced gene conversion and sister-chromatid exchange events. Tauchi et al. used a site-specific enzyme (I-SceI) to create a DSB and demonstrated that the homologous recombination repair pathway required a functional Nbs1 protein.