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Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing
Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda–sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A pre...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397184/ https://www.ncbi.nlm.nih.gov/pubmed/28168278 http://dx.doi.org/10.1093/nar/gkx081 |
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author | Kim, Jin S. Nanfara, Michael T. Chodavarapu, Sundari Jin, Kyeong S. Babu, Vignesh M. P. Ghazy, Mohamed A. Chung, Scisung Kaguni, Jon M. Sutton, Mark D. Cho, Yunje |
author_facet | Kim, Jin S. Nanfara, Michael T. Chodavarapu, Sundari Jin, Kyeong S. Babu, Vignesh M. P. Ghazy, Mohamed A. Chung, Scisung Kaguni, Jon M. Sutton, Mark D. Cho, Yunje |
author_sort | Kim, Jin S. |
collection | PubMed |
description | Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda–sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda–β clamp complex. This complex contains two pairs of Hda dimers sandwiched between two β clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the β clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda–β clamp complex indicate that the interaction of the β clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda–β clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function. |
format | Online Article Text |
id | pubmed-5397184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53971842017-04-24 Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing Kim, Jin S. Nanfara, Michael T. Chodavarapu, Sundari Jin, Kyeong S. Babu, Vignesh M. P. Ghazy, Mohamed A. Chung, Scisung Kaguni, Jon M. Sutton, Mark D. Cho, Yunje Nucleic Acids Res Genome Integrity, Repair and Replication Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda–sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda–β clamp complex. This complex contains two pairs of Hda dimers sandwiched between two β clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the β clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda–β clamp complex indicate that the interaction of the β clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda–β clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function. Oxford University Press 2017-04-20 2017-02-07 /pmc/articles/PMC5397184/ /pubmed/28168278 http://dx.doi.org/10.1093/nar/gkx081 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Genome Integrity, Repair and Replication Kim, Jin S. Nanfara, Michael T. Chodavarapu, Sundari Jin, Kyeong S. Babu, Vignesh M. P. Ghazy, Mohamed A. Chung, Scisung Kaguni, Jon M. Sutton, Mark D. Cho, Yunje Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing |
title | Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing |
title_full | Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing |
title_fullStr | Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing |
title_full_unstemmed | Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing |
title_short | Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing |
title_sort | dynamic assembly of hda and the sliding clamp in the regulation of replication licensing |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397184/ https://www.ncbi.nlm.nih.gov/pubmed/28168278 http://dx.doi.org/10.1093/nar/gkx081 |
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