Mutator genes for suppression of gross chromosomal rearrangements identified by a genome-wide screening in Saccharomyces cerevisiae

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Abstract
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.