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A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase

Cohesin complex mediates cohesion between sister chromatids, which promotes high-fidelity chromosome segregation. Eco1p acetylates the cohesin subunit Smc3p during S phase to establish cohesion. The current model posits that this Eco1p-mediated acetylation promotes establishment by abrogating the ab...

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Autores principales: Guacci, Vincent, Stricklin, Jeremiah, Bloom, Michelle S., Guō, Xuánzōng, Bhatter, Meghna, Koshland, Douglas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279223/
https://www.ncbi.nlm.nih.gov/pubmed/25378582
http://dx.doi.org/10.1091/mbc.E14-08-1268
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author Guacci, Vincent
Stricklin, Jeremiah
Bloom, Michelle S.
Guō, Xuánzōng
Bhatter, Meghna
Koshland, Douglas
author_facet Guacci, Vincent
Stricklin, Jeremiah
Bloom, Michelle S.
Guō, Xuánzōng
Bhatter, Meghna
Koshland, Douglas
author_sort Guacci, Vincent
collection PubMed
description Cohesin complex mediates cohesion between sister chromatids, which promotes high-fidelity chromosome segregation. Eco1p acetylates the cohesin subunit Smc3p during S phase to establish cohesion. The current model posits that this Eco1p-mediated acetylation promotes establishment by abrogating the ability of Wpl1p to destabilize cohesin binding to chromosomes. Here we present data from budding yeast that is incompatible with this Wpl1p-centric model. Two independent in vivo assays show that a wpl1∆ fails to suppress cohesion defects of eco1∆ cells. Moreover, a wpl1∆ also fails to suppress cohesion defects engendered by blocking just the essential Eco1p acetylation sites on Smc3p (K112, K113). Thus removing WPL1 inhibition is insufficient for generating cohesion without ECO1 activity. To elucidate how ECO1 promotes cohesion, we conducted a genetic screen and identified a cohesion activator mutation in the SMC3 head domain (D1189H). Smc3-D1189H partially restores cohesion in eco1∆ wpl1∆ or eco1 mutant cells but robustly restores cohesion in cells blocked for Smc3p K112 K113 acetylation. These data support two important conclusions. First, acetylation of the K112 K113 region by Eco1p promotes cohesion establishment by altering Smc3p head function independent of its ability to antagonize Wpl1p. Second, Eco1p targets other than Smc3p K112 K113 are necessary for efficient establishment.
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spelling pubmed-42792232015-03-16 A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase Guacci, Vincent Stricklin, Jeremiah Bloom, Michelle S. Guō, Xuánzōng Bhatter, Meghna Koshland, Douglas Mol Biol Cell Articles Cohesin complex mediates cohesion between sister chromatids, which promotes high-fidelity chromosome segregation. Eco1p acetylates the cohesin subunit Smc3p during S phase to establish cohesion. The current model posits that this Eco1p-mediated acetylation promotes establishment by abrogating the ability of Wpl1p to destabilize cohesin binding to chromosomes. Here we present data from budding yeast that is incompatible with this Wpl1p-centric model. Two independent in vivo assays show that a wpl1∆ fails to suppress cohesion defects of eco1∆ cells. Moreover, a wpl1∆ also fails to suppress cohesion defects engendered by blocking just the essential Eco1p acetylation sites on Smc3p (K112, K113). Thus removing WPL1 inhibition is insufficient for generating cohesion without ECO1 activity. To elucidate how ECO1 promotes cohesion, we conducted a genetic screen and identified a cohesion activator mutation in the SMC3 head domain (D1189H). Smc3-D1189H partially restores cohesion in eco1∆ wpl1∆ or eco1 mutant cells but robustly restores cohesion in cells blocked for Smc3p K112 K113 acetylation. These data support two important conclusions. First, acetylation of the K112 K113 region by Eco1p promotes cohesion establishment by altering Smc3p head function independent of its ability to antagonize Wpl1p. Second, Eco1p targets other than Smc3p K112 K113 are necessary for efficient establishment. The American Society for Cell Biology 2015-01-01 /pmc/articles/PMC4279223/ /pubmed/25378582 http://dx.doi.org/10.1091/mbc.E14-08-1268 Text en © 2015 Guacci et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Guacci, Vincent
Stricklin, Jeremiah
Bloom, Michelle S.
Guō, Xuánzōng
Bhatter, Meghna
Koshland, Douglas
A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase
title A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase
title_full A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase
title_fullStr A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase
title_full_unstemmed A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase
title_short A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase
title_sort novel mechanism for the establishment of sister chromatid cohesion by the eco1 acetyltransferase
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279223/
https://www.ncbi.nlm.nih.gov/pubmed/25378582
http://dx.doi.org/10.1091/mbc.E14-08-1268
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