title: Mechanism of Regulation of Intrachromatid Recombination and Long-Range Chromosome Interactions in Saccharomyces cerevisiae.
abstract: The NAD-dependent histone deacetylase Sir2 controls ribosomal DNA (rDNA) silencing by inhibiting recombination and RNA polymerase II-catalyzed transcription in the rDNA of Saccharomyces cerevisiae Sir2 is recruited to nontranscribed spacer 1 (NTS1) of the rDNA array by interaction between the RENT ( RE: gulation of N: ucleolar S: ilencing and T: elophase exit) complex and the replication terminator protein Fob1. The latter binds to its cognate sites, called replication termini (Ter) or replication fork barriers (RFB), that are located in each copy of NTS1. This work provides new mechanistic insights into the regulation of rDNA silencing and intrachromatid recombination by showing that Sir2 recruitment is stringently regulated by Fob1 phosphorylation at specific sites in its C-terminal domain (C-Fob1), which also regulates long-range Ter-Ter interactions. We show further that long-range Fob1-mediated Ter-Ter interactions in trans are downregulated by Sir2. These regulatory mechanisms control intrachromatid recombination and the replicative life span (RLS).
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Shamsu
authors.initials: S
authors.lastname: Zaman
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Malay
authors.initials: M
authors.lastname: Choudhury
authors.affiliation: Department of Medicine and Tulane Center for Aging, Tulane University, New Orleans, Louisiana, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Srivastava
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Bidyut K
authors.initials: BK
authors.lastname: Mohanty
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Danielson
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Humphrey
authors.affiliation: Department of Medicine and Tulane Center for Aging, Tulane University, New Orleans, Louisiana, USA sjazwins@tulane.edu bastia@musc.edu.
authors.forename: S Michal
authors.initials: SM
authors.lastname: Jazwinski
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA sjazwins@tulane.edu bastia@musc.edu.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bastia
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D002842:Chromatids / Q000235:genetics*; D015825:Chromosomes, Fungal / Q000235:genetics; D004275:DNA, Ribosomal / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D056565:Sirtuin 2 / Q000737:chemistry / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C105579:FOB1 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; C119300:Net1 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C119637:TOF2 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2