Tying up loose ends: nonhomologous end-joining in Saccharomyces cerevisiae

The ends of chromosomal DNA double-strand breaks (DSBs) can be accurately r ejoined by at least two discrete pathways, homologous recombination and non homologous end-joining (NHEJ). The NHEJ pathway is essential for repair of specific classes of DSB termini in cells of the budding yeast Saccharomyces cerevisiae. Endonuclease-induced DSBs retaining complementary single-stran ded DNA overhangs are repaired efficiently by end-joining. In contrast, dam aged DSB ends (e.g., termini produced by ionizing radiation) are poor subst rates for this pathway. NHEJ repair involves the functions of at least 10 g enes, including YKU70, YKU80, DNL4, LIF1, SIR2, SIR3, SIR4, RAD50, MRE11, a nd XRS2. Most or all of these genes are required for efficient recombinatio n-independent recircularization of linearized plasmids and for rejoining of EcoRI endonuclease-induced chromosomal DSBs in vivo. Several NHEJ mutants also display aberrant processing and rejoining of DSBs that are generated b y HO endonuclease or formed spontaneously in dicentric plasmids. In additio n, all NHEJ genes except DNL4 and LIF1 are required for stabilization of te lomeric repeat sequences. Each of the proteins involved in NHEJ appears to bind, directly or through protein associations, with the ends of linear DNA . Enzymatic and/or structural roles in the rejoining of DSB termini have be en postulated for several proteins within the group. Most yeast NHEJ genes have homologues in human cells and many biochemical activities and protein: protein interactions have been conserved in higher eucaryotes. Similarities and differences between NHEJ repair in yeast and mammalian cells are discu ssed. Published by Elsevier Science B.V.