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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| Format: | Article |
| Language: | en_US |
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American Society for Cell Biology
2015
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| Online Access: | http://hdl.handle.net/1721.1/92588 |
| _version_ | 1826207472224829440 |
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| author | Guacci, Vincent Stricklin, Jeremiah Bloom, Michelle S. Guo, Xuanzong Bhatter, Meghna Koshland, Douglas |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Guacci, Vincent Stricklin, Jeremiah Bloom, Michelle S. Guo, Xuanzong Bhatter, Meghna Koshland, Douglas |
| author_sort | Guacci, Vincent |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T13:50:11Z |
| format | Article |
| id | mit-1721.1/92588 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:50:11Z |
| publishDate | 2015 |
| publisher | American Society for Cell Biology |
| record_format | dspace |
| spelling | mit-1721.1/925882022-09-28T16:28:32Z A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase Guacci, Vincent Stricklin, Jeremiah Bloom, Michelle S. Guo, Xuanzong Bhatter, Meghna Koshland, Douglas Massachusetts Institute of Technology. Department of Biology Guo, Xuanzong 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. National Institutes of Health (U.S.) (Grant R01GM092813) 2015-01-05T18:10:41Z 2015-01-05T18:10:41Z 2014-10 2014-11 Article http://purl.org/eprint/type/JournalArticle 1059-1524 1939-4586 http://hdl.handle.net/1721.1/92588 Guacci, Vincent, Jeremiah Stricklin, Michelle S. Bloom, Xuanzong Guo, Meghna Bhatter, and Douglas Koshland. “A Novel Mechanism for the Establishment of Sister Chromatid Cohesion by the ECO1 Acetyl-Transferase.” Molecular Biology of the Cell (November 5, 2014). en_US http://dx.doi.org/10.1091/mbc.E14-08-1268 Molecular Biology of the Cell Creative Commons Attribution http://creativecommons.org/licenses/by-nc-sa/3.0 application/pdf American Society for Cell Biology American Society for Cell Biology |
| spellingShingle | Guacci, Vincent Stricklin, Jeremiah Bloom, Michelle S. Guo, Xuanzong 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 |
| url | http://hdl.handle.net/1721.1/92588 |
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