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Structural evidence for Scc4-dependent localization of cohesin loading

The cohesin ring holds newly replicated sister chromatids together until their separation at anaphase. Initiation of sister chromatid cohesion depends on a separate complex, Scc2(NIPBL)/Scc4(Mau2) (Scc2/4), which loads cohesin onto DNA and determines its localization across the genome. Proper cohesi...

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Autores principales: Hinshaw, Stephen M, Makrantoni, Vasso, Kerr, Alastair, Marston, Adèle L, Harrison, Stephen C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471937/
https://www.ncbi.nlm.nih.gov/pubmed/26038942
http://dx.doi.org/10.7554/eLife.06057
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author Hinshaw, Stephen M
Makrantoni, Vasso
Kerr, Alastair
Marston, Adèle L
Harrison, Stephen C
author_facet Hinshaw, Stephen M
Makrantoni, Vasso
Kerr, Alastair
Marston, Adèle L
Harrison, Stephen C
author_sort Hinshaw, Stephen M
collection PubMed
description The cohesin ring holds newly replicated sister chromatids together until their separation at anaphase. Initiation of sister chromatid cohesion depends on a separate complex, Scc2(NIPBL)/Scc4(Mau2) (Scc2/4), which loads cohesin onto DNA and determines its localization across the genome. Proper cohesin loading is essential for cell division, and partial defects cause chromosome missegregation and aberrant transcriptional regulation, leading to severe developmental defects in multicellular organisms. We present here a crystal structure showing the interaction between Scc2 and Scc4. Scc4 is a TPR array that envelops an extended Scc2 peptide. Using budding yeast, we demonstrate that a conserved patch on the surface of Scc4 is required to recruit Scc2/4 to centromeres and to build pericentromeric cohesion. These findings reveal the role of Scc4 in determining the localization of cohesin loading and establish a molecular basis for Scc2/4 recruitment to centromeres. DOI: http://dx.doi.org/10.7554/eLife.06057.001
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spelling pubmed-44719372015-06-19 Structural evidence for Scc4-dependent localization of cohesin loading Hinshaw, Stephen M Makrantoni, Vasso Kerr, Alastair Marston, Adèle L Harrison, Stephen C eLife Biophysics and Structural Biology The cohesin ring holds newly replicated sister chromatids together until their separation at anaphase. Initiation of sister chromatid cohesion depends on a separate complex, Scc2(NIPBL)/Scc4(Mau2) (Scc2/4), which loads cohesin onto DNA and determines its localization across the genome. Proper cohesin loading is essential for cell division, and partial defects cause chromosome missegregation and aberrant transcriptional regulation, leading to severe developmental defects in multicellular organisms. We present here a crystal structure showing the interaction between Scc2 and Scc4. Scc4 is a TPR array that envelops an extended Scc2 peptide. Using budding yeast, we demonstrate that a conserved patch on the surface of Scc4 is required to recruit Scc2/4 to centromeres and to build pericentromeric cohesion. These findings reveal the role of Scc4 in determining the localization of cohesin loading and establish a molecular basis for Scc2/4 recruitment to centromeres. DOI: http://dx.doi.org/10.7554/eLife.06057.001 eLife Sciences Publications, Ltd 2015-06-03 /pmc/articles/PMC4471937/ /pubmed/26038942 http://dx.doi.org/10.7554/eLife.06057 Text en © 2015, Hinshaw et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Hinshaw, Stephen M
Makrantoni, Vasso
Kerr, Alastair
Marston, Adèle L
Harrison, Stephen C
Structural evidence for Scc4-dependent localization of cohesin loading
title Structural evidence for Scc4-dependent localization of cohesin loading
title_full Structural evidence for Scc4-dependent localization of cohesin loading
title_fullStr Structural evidence for Scc4-dependent localization of cohesin loading
title_full_unstemmed Structural evidence for Scc4-dependent localization of cohesin loading
title_short Structural evidence for Scc4-dependent localization of cohesin loading
title_sort structural evidence for scc4-dependent localization of cohesin loading
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471937/
https://www.ncbi.nlm.nih.gov/pubmed/26038942
http://dx.doi.org/10.7554/eLife.06057
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