Cargando…
Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation
BACKGROUND: Cohesin mediates sister chromatid cohesion by topologically entrapping sister DNA molecules inside its ring structure. Cohesin is loaded onto DNA by the Scc2/NIPBL-Scc4/MAU2-loading complex in a manner that depends on the adenosine triphosphatase (ATPase) activity of cohesin’s Smc1 and S...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188815/ https://www.ncbi.nlm.nih.gov/pubmed/25220052 http://dx.doi.org/10.1016/j.cub.2014.08.011 |
_version_ | 1782338273475035136 |
---|---|
author | Ladurner, Rene Bhaskara, Venugopal Huis in ’t Veld, Pim J. Davidson, Iain F. Kreidl, Emanuel Petzold, Georg Peters, Jan-Michael |
author_facet | Ladurner, Rene Bhaskara, Venugopal Huis in ’t Veld, Pim J. Davidson, Iain F. Kreidl, Emanuel Petzold, Georg Peters, Jan-Michael |
author_sort | Ladurner, Rene |
collection | PubMed |
description | BACKGROUND: Cohesin mediates sister chromatid cohesion by topologically entrapping sister DNA molecules inside its ring structure. Cohesin is loaded onto DNA by the Scc2/NIPBL-Scc4/MAU2-loading complex in a manner that depends on the adenosine triphosphatase (ATPase) activity of cohesin’s Smc1 and Smc3 subunits. Subsequent cohesion establishment during DNA replication depends on Smc3 acetylation by Esco1 and Esco2 and on recruitment of sororin, which “locks” cohesin on DNA by inactivating the cohesin release factor Wapl. RESULTS: Human cohesin ATPase mutants associate transiently with DNA in a manner that depends on the loading complex but cannot be stabilized on chromatin by depletion of Wapl. These mutants cannot be acetylated, fail to interact with sororin, and do not mediate cohesion. The absence of Smc3 acetylation in the ATPase mutants is not a consequence of their transient association with DNA but is directly caused by their inability to hydrolyze ATP because acetylation of wild-type cohesin also depends on ATP hydrolysis. CONCLUSIONS: Our data indicate that cohesion establishment involves the following steps. First, cohesin transiently associates with DNA in a manner that depends on the loading complex. Subsequently, ATP hydrolysis by cohesin leads to entrapment of DNA and converts Smc3 into a state that can be acetylated. Finally, Smc3 acetylation leads to recruitment of sororin, inhibition of Wapl, and stabilization of cohesin on DNA. Our finding that cohesin’s ATPase activity is required for both cohesin loading and Smc3 acetylation raises the possibility that cohesion establishment is directly coupled to the reaction in which cohesin entraps DNA. |
format | Online Article Text |
id | pubmed-4188815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41888152014-10-13 Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation Ladurner, Rene Bhaskara, Venugopal Huis in ’t Veld, Pim J. Davidson, Iain F. Kreidl, Emanuel Petzold, Georg Peters, Jan-Michael Curr Biol Article BACKGROUND: Cohesin mediates sister chromatid cohesion by topologically entrapping sister DNA molecules inside its ring structure. Cohesin is loaded onto DNA by the Scc2/NIPBL-Scc4/MAU2-loading complex in a manner that depends on the adenosine triphosphatase (ATPase) activity of cohesin’s Smc1 and Smc3 subunits. Subsequent cohesion establishment during DNA replication depends on Smc3 acetylation by Esco1 and Esco2 and on recruitment of sororin, which “locks” cohesin on DNA by inactivating the cohesin release factor Wapl. RESULTS: Human cohesin ATPase mutants associate transiently with DNA in a manner that depends on the loading complex but cannot be stabilized on chromatin by depletion of Wapl. These mutants cannot be acetylated, fail to interact with sororin, and do not mediate cohesion. The absence of Smc3 acetylation in the ATPase mutants is not a consequence of their transient association with DNA but is directly caused by their inability to hydrolyze ATP because acetylation of wild-type cohesin also depends on ATP hydrolysis. CONCLUSIONS: Our data indicate that cohesion establishment involves the following steps. First, cohesin transiently associates with DNA in a manner that depends on the loading complex. Subsequently, ATP hydrolysis by cohesin leads to entrapment of DNA and converts Smc3 into a state that can be acetylated. Finally, Smc3 acetylation leads to recruitment of sororin, inhibition of Wapl, and stabilization of cohesin on DNA. Our finding that cohesin’s ATPase activity is required for both cohesin loading and Smc3 acetylation raises the possibility that cohesion establishment is directly coupled to the reaction in which cohesin entraps DNA. Cell Press 2014-10-06 /pmc/articles/PMC4188815/ /pubmed/25220052 http://dx.doi.org/10.1016/j.cub.2014.08.011 Text en © 2014 The Authors https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) . |
spellingShingle | Article Ladurner, Rene Bhaskara, Venugopal Huis in ’t Veld, Pim J. Davidson, Iain F. Kreidl, Emanuel Petzold, Georg Peters, Jan-Michael Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation |
title | Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation |
title_full | Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation |
title_fullStr | Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation |
title_full_unstemmed | Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation |
title_short | Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation |
title_sort | cohesin’s atpase activity couples cohesin loading onto dna with smc3 acetylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188815/ https://www.ncbi.nlm.nih.gov/pubmed/25220052 http://dx.doi.org/10.1016/j.cub.2014.08.011 |
work_keys_str_mv | AT ladurnerrene cohesinsatpaseactivitycouplescohesinloadingontodnawithsmc3acetylation AT bhaskaravenugopal cohesinsatpaseactivitycouplescohesinloadingontodnawithsmc3acetylation AT huisintveldpimj cohesinsatpaseactivitycouplescohesinloadingontodnawithsmc3acetylation AT davidsoniainf cohesinsatpaseactivitycouplescohesinloadingontodnawithsmc3acetylation AT kreidlemanuel cohesinsatpaseactivitycouplescohesinloadingontodnawithsmc3acetylation AT petzoldgeorg cohesinsatpaseactivitycouplescohesinloadingontodnawithsmc3acetylation AT petersjanmichael cohesinsatpaseactivitycouplescohesinloadingontodnawithsmc3acetylation |