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Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance

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 pr...

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Autores principales: Choudhury, Malay, Zaman, Shamsu, Jiang, James C., Jazwinski, S. Michal, Bastia, Deepak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470286/
https://www.ncbi.nlm.nih.gov/pubmed/26063576
http://dx.doi.org/10.1101/gad.260844.115
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author Choudhury, Malay
Zaman, Shamsu
Jiang, James C.
Jazwinski, S. Michal
Bastia, Deepak
author_facet Choudhury, Malay
Zaman, Shamsu
Jiang, James C.
Jazwinski, S. Michal
Bastia, Deepak
author_sort Choudhury, Malay
collection PubMed
description 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.
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spelling pubmed-44702862015-12-01 Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance Choudhury, Malay Zaman, Shamsu Jiang, James C. Jazwinski, S. Michal Bastia, Deepak Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2015-06-01 /pmc/articles/PMC4470286/ /pubmed/26063576 http://dx.doi.org/10.1101/gad.260844.115 Text en © 2015 Choudhury et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Choudhury, Malay
Zaman, Shamsu
Jiang, James C.
Jazwinski, S. Michal
Bastia, Deepak
Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance
title Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance
title_full Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance
title_fullStr Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance
title_full_unstemmed Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance
title_short Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance
title_sort mechanism of regulation of ‘chromosome kissing’ induced by fob1 and its physiological significance
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470286/
https://www.ncbi.nlm.nih.gov/pubmed/26063576
http://dx.doi.org/10.1101/gad.260844.115
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