title: Involvement of Sir2/4 in silencing of DNA breakage and recombination on mouse YACs during yeast meiosis.
abstract: Yeast artificial chromosomes (YACs) that contain human DNA backbone undergo DNA double-strand breaks (DSBs) and recombination during yeast meiosis at rates similar to the yeast native chromosomes. Surprisingly, YACs containing DNA covering a recombination hot spot in the mouse major histocompatibility complex class III region do not show meiotic DSBs and undergo meiotic recombination at reduced levels. Moreover, segregation of these YACs during meiosis is seriously compromised. In meiotic yeast cells carrying the mutations sir2 or sir4, but not sir3, these YACs show DSBs, suggesting that a unique chromatin structure of the YACs, involving Sir2 and Sir4, protects the YACs from the meiotic recombination machinery. We speculate that the paucity of DSBs and recombination events on these YACs during yeast meiosis may reflect the refractory nature of the corresponding region in the mouse genome.
authors.affiliation: Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Klieger
authors.forename: Ofer
authors.initials: O
authors.lastname: Yizhar
authors.forename: Drora
authors.initials: D
authors.lastname: Zenvirth
authors.forename: Neta
authors.initials: N
authors.lastname: Shtepel-Milman
authors.forename: Margriet
authors.initials: M
authors.lastname: Snoek
authors.forename: Giora
authors.initials: G
authors.lastname: Simchen
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry; D002875:Chromosomes / Q000235:genetics; D018244:Chromosomes, Artificial, Yeast; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D020868:Gene Silencing; D016678:Genome; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D008540:Meiosis; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000502:physiology*
chemical_list: D002843:Chromatin; C084122:SIR3 protein, S cerevisiae; C061573:SIR4 protein, S cerevisiae; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D004247:DNA; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases