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Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1

RCC1 is the only known exchange factor for the Ran guanosine triphosphatase and performs essential roles in nuclear transport, spindle organization, and nuclear envelope formation. RCC1 binds to chromatin through a bimodal attachment to DNA and histones, and defects in binding cause chromosome misse...

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Detalles Bibliográficos
Autores principales: Hao, Yi, Macara, Ian G.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528582/
https://www.ncbi.nlm.nih.gov/pubmed/18762580
http://dx.doi.org/10.1083/jcb.200803110
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author Hao, Yi
Macara, Ian G.
author_facet Hao, Yi
Macara, Ian G.
author_sort Hao, Yi
collection PubMed
description RCC1 is the only known exchange factor for the Ran guanosine triphosphatase and performs essential roles in nuclear transport, spindle organization, and nuclear envelope formation. RCC1 binds to chromatin through a bimodal attachment to DNA and histones, and defects in binding cause chromosome missegregation. Chromatin binding is enhanced by apo-Ran. However, the mechanism underlying this regulation has been unclear. We now demonstrate that the N-terminal tail of RCC1 is essential for association with DNA but inhibits histone binding. Apo-Ran significantly promotes RCC1 binding to both DNA and histones, and these effects are tail mediated. Using a fluorescence resonance energy transfer biosensor, we detect conformational changes in the tail of RCC1 coupled to the two binding modes and in response to interactions with Ran and importin-α. The biosensor also reports changes accompanying mitosis in living cells. We propose that Ran induces an allosteric conformational switch in the tail that exposes the histone-binding surface on RCC1 and facilitates association of the positively charged tail with DNA.
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spelling pubmed-25285822009-03-08 Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1 Hao, Yi Macara, Ian G. J Cell Biol Research Articles RCC1 is the only known exchange factor for the Ran guanosine triphosphatase and performs essential roles in nuclear transport, spindle organization, and nuclear envelope formation. RCC1 binds to chromatin through a bimodal attachment to DNA and histones, and defects in binding cause chromosome missegregation. Chromatin binding is enhanced by apo-Ran. However, the mechanism underlying this regulation has been unclear. We now demonstrate that the N-terminal tail of RCC1 is essential for association with DNA but inhibits histone binding. Apo-Ran significantly promotes RCC1 binding to both DNA and histones, and these effects are tail mediated. Using a fluorescence resonance energy transfer biosensor, we detect conformational changes in the tail of RCC1 coupled to the two binding modes and in response to interactions with Ran and importin-α. The biosensor also reports changes accompanying mitosis in living cells. We propose that Ran induces an allosteric conformational switch in the tail that exposes the histone-binding surface on RCC1 and facilitates association of the positively charged tail with DNA. The Rockefeller University Press 2008-09-08 /pmc/articles/PMC2528582/ /pubmed/18762580 http://dx.doi.org/10.1083/jcb.200803110 Text en © 2008 Hao and Macara This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Hao, Yi
Macara, Ian G.
Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1
title Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1
title_full Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1
title_fullStr Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1
title_full_unstemmed Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1
title_short Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1
title_sort regulation of chromatin binding by a conformational switch in the tail of the ran exchange factor rcc1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528582/
https://www.ncbi.nlm.nih.gov/pubmed/18762580
http://dx.doi.org/10.1083/jcb.200803110
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