title: Mechanism of regulation of 'chromosome kissing' induced by Fob1 and its physiological significance.
abstract: Protein-mediated "chromosome kissing" between two DNA sites in trans (or in cis) is known to facilitate three-dimensional control of gene expression and DNA replication. However, the mechanisms of regulation of the long-range interactions are unknown. Here, we show that the replication terminator protein Fob1 of Saccharomyces cerevisiae promoted chromosome kissing that initiated rDNA recombination and controlled the replicative life span (RLS). Oligomerization of Fob1 caused synaptic (kissing) interactions between pairs of terminator (Ter) sites that initiated recombination in rDNA. Fob1 oligomerization and Ter-Ter kissing were regulated by intramolecular inhibitory interactions between the C-terminal domain (C-Fob1) and the N-terminal domain (N-Fob1). Phosphomimetic substitutions of specific residues of C-Fob1 counteracted the inhibitory interaction. A mutation in either N-Fob1 that blocked Fob1 oligomerization or C-Fob1 that blocked its phosphorylation antagonized chromosome kissing and recombination and enhanced the RLS. The results provide novel insights into a mechanism of regulation of Fob1-mediated chromosome kissing.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA;
authors.forename: Malay
authors.initials: M
authors.lastname: Choudhury
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA;
authors.forename: Shamsu
authors.initials: S
authors.lastname: Zaman
authors.affiliation: Tulane Center for Aging, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Jiang
authors.affiliation: Tulane Center for Aging, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
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 29425, USA; bastia@musc.edu.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bastia
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C105579:FOB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: autoinhibitory control; chromosome kissing; protein oligomerization; recombination; replication termination; replication terminator protein; replicative life span