title: Differential genetic interactions between Sgs1, DNA-damage checkpoint components and DNA repair factors in the maintenance of chromosome stability.
abstract: BACKGROUND
  Genome instability is associated with human cancers and chromosome breakage syndromes, including Bloom's syndrome, caused by inactivation of BLM helicase. Numerous mutations that lead to genome instability are known, yet how they interact genetically is poorly understood.
  
  
  RESULTS
  We show that spontaneous translocations that arise by nonallelic homologous recombination in DNA-damage-checkpoint-defective yeast lacking the BLM-related Sgs1 helicase (sgs1Δ mec3Δ) are inhibited if cells lack Mec1/ATR kinase. Tel1/ATM, in contrast, acts as a suppressor independently of Mec3 and Sgs1. Translocations are also inhibited in cells lacking Dun1 kinase, but not in cells defective in a parallel checkpoint branch defined by Chk1 kinase. While we had previously shown that RAD51 deletion did not inhibit translocation formation, RAD59 deletion led to inhibition comparable to the rad52Δ mutation. A candidate screen of other DNA metabolic factors identified Exo1 as a strong suppressor of chromosomal rearrangements in the sgs1Δ mutant, becoming even more important for chromosomal stability upon MEC3 deletion. We determined that the C-terminal third of Exo1, harboring mismatch repair protein binding sites and phosphorylation sites, is dispensable for Exo1's roles in chromosomal rearrangement suppression, mutation avoidance and resistance to DNA-damaging agents.
  
  
  CONCLUSIONS
  Our findings suggest that translocations between related genes can form by Rad59-dependent, Rad51-independent homologous recombination, which is independently suppressed by Sgs1, Tel1, Mec3 and Exo1 but promoted by Dun1 and the telomerase-inhibitor Mec1. We propose a model for the functional interaction between mitotic recombination and the DNA-damage checkpoint in the suppression of chromosomal rearrangements in sgs1Δ cells.
authors: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA.
authors: Lillian
authors: L
authors: Doerfler
authors: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA.
authors: Lorena
authors: L
authors: Harris
authors: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA.
authors: Emilie
authors: E
authors: Viebranz
authors: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA.
authors: Kristina H
authors: KH
authors: Schmidt