Different types of gross chromosomal rearrangements (GCRs), including translocations, interstitial deletions, terminal deletions with de novo telomere additions, and chromosome fusions, are observed in many cancers. Multiple pathways, such as S-phase checkpoints, DNA replication, recombination, chromatin remodeling, and telomere maintenance that suppress GCRs have been identified. To experimentally expand our knowledge of other pathway(s) that suppress GCRs, we developed a generally applicable genome-wide screening method. In this screen, we identified 10 genes ( ALO1, CDC50, CSM2, ELG1, ESC1, MMS4, RAD5, RAD18, TSA1 , and UFO1 ) that encode proteins functioning in the suppression of GCRs. Moreover, the breakpoint junctions of GCRs from these GCR mutator mutants were determined with modified breakpoint-mapping methods. We also identified nine genes ( AKR1, BFR1, HTZ1, IES6, NPL6, RPL13B, RPL27A, RPL35A , and SHU2 ) whose mutations generated growth defects with the pif1 Δ mutation. In addition, we found that some of these mutations changed the telomere size.