title: Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications.
abstract: Translocations in chromosomes alter genetic information. Although the frequent translocations observed in many tumors suggest the altered genetic information by translocation could promote tumorigenesis, the mechanisms for how translocations are suppressed and produced are poorly understood. The smc6-9 mutation increased the translocation class gross chromosomal rearrangement (GCR). Translocations produced in the smc6-9 strain are unique because they are non-reciprocal and dependent on break-induced replication (BIR) and independent of non-homologous end joining. The high incidence of translocations near repetitive sequences such as delta sequences, ARS, tRNA genes, and telomeres in the smc6-9 strain indicates that Smc5-Smc6 suppresses translocations by reducing DNA damage at repetitive sequences. Synergistic enhancements of translocations in strains defective in DNA damage checkpoints by the smc6-9 mutation without affecting de novo telomere addition class GCR suggest that Smc5-Smc6 defines a new pathway to suppress GCR formation.
authors.affiliation: Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892 USA.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Hwang
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith
authors.forename: Audrey
authors.initials: A
authors.lastname: Ceschia
authors.forename: Jordi
authors.initials: J
authors.lastname: Torres-Rosell
authors.forename: Luis
authors.initials: L
authors.lastname: Aragon
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Myung
mesh_terms: D018797:Cell Cycle Proteins / Q000502:physiology*; D002869:Chromosome Aberrations; D004249:DNA Damage; D004261:DNA Replication; D012091:Repetitive Sequences, Nucleic Acid; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D016615:Telomere / Q000502:physiology; D014178:Translocation, Genetic
chemical_list: D018797:Cell Cycle Proteins; C486627:SMC5 protein, S cerevisiae; C486631:SMC6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins