title: The Rad1-Rad10 complex promotes the production of gross chromosomal rearrangements from spontaneous DNA damage in Saccharomyces cerevisiae.
abstract: Gross chromosomal rearrangements (GCRs) have been observed in many cancers. Previously, we have demonstrated many mechanisms for suppression of GCR formation in yeast. However, pathways that promote the formation of GCRs are not as well understood. Here, we present evidence that the Rad1-Rad10 endonuclease, which plays an important role in nucleotide excision and recombination repairs, has a novel role to produce GCRs. A mutation of either the RAD1 or the RAD10 gene reduced GCR rates in many GCR mutator strains. The inactivation of Rad1 or Rad10 in GCR mutator strains also slightly enhanced methyl methanesulfonate sensitivity. Although the GCRs induced by treatment with DNA-damaging agents were not reduced by rad1 or rad10 mutations, the translocation- and deletion-type GCRs created by a single double-strand break are mostly replaced by de novo telomere-addition-type GCR. Results presented here suggest that Rad1-Rad10 functions at different stages of GCR formation and that there is an alternative pathway for the GCR formation that is independent of Rad1-Rad10.
authors.affiliation: Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Hwang
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Myung
mesh_terms: D002875:Chromosomes / Q000648:ultrastructure*; D003433:Crosses, Genetic; D004249:DNA Damage; D045643:DNA Repair Enzymes; D004277:DNA, Single-Stranded / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D017353:Gene Deletion; D005821:Genetic Techniques; D005838:Genotype; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008957:Models, Genetic; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015719:Single-Strand Specific DNA and RNA Endonucleases
chemical_list: D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D004720:Endonucleases; C069266:RAD1 protein, S cerevisiae; C064162:RAD10 protein, S cerevisiae; D015719:Single-Strand Specific DNA and RNA Endonucleases; D045643:DNA Repair Enzymes