Long-range DNA end resection supports homologous recombination by checkpoint activation rather than extensive homology generation

Abstract

Homologous recombination (HR), the error-free mechanism for double-strand break (DSB) repair, relies on DNA end resection by nucleolytic degradation of the 5'-terminated ends. However, the role of long-range resection mediated by Exo1 and/or Sgs1-Dna2 in HR is not fully understood. Here, we show that Exo1 and Sgs1 are dispensable for recombination between closely-linked repeats but are required for interchromosomal repeat recombination in Saccharomyces cerevisiae. This requirement for long-range resection is coupled to DNA damage checkpoint activation and the need for checkpoint proteins. Furthermore, artificial activation of the checkpoint partially restores interchromosomal recombination to exo1{Delta} sgs1{Delta} cells. However, cell cycle delay is insufficient to rescue the interchromosomal recombination defect of exo1{Delta} sgs1{Delta} cells, suggesting an additional role for the checkpoint. Given that the checkpoint is necessary for DNA damage-induced chromosome mobility, we propose that the importance of the checkpoint, and therefore long-range resection, in interchromosomal recombination is due to a need to increase chromosome mobility to facilitate pairing of distant sites. The need for long-range resection is circumvented when the DSB and its repair template are in close proximity.