Control of the replication initiator DnaA by an anti-cooperativity factor

Proper coordination of DNA replication with cell growth and division is critical for production of viable progeny. In bacteria, coordination of DNA replication with cell growth is generally achieved by controlling activity of the replication initiator DnaA and its access to the chromosomal origin of...

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Main Author: Merrikh, Houra
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: John Wiley & Sons, Inc. 2012
Online Access:http://hdl.handle.net/1721.1/74105
https://orcid.org/0000-0002-8235-7227
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author Merrikh, Houra
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Merrikh, Houra
author_sort Merrikh, Houra
collection MIT
description Proper coordination of DNA replication with cell growth and division is critical for production of viable progeny. In bacteria, coordination of DNA replication with cell growth is generally achieved by controlling activity of the replication initiator DnaA and its access to the chromosomal origin of replication, oriC. Here we describe a previously unknown mechanism for regulation of DnaA. YabA, a negative regulator of replication initiation in Bacillus subtilis, interacts with DnaA and DnaN, the sliding (processivity) clamp of DNA polymerase. We found that in vivo, YabA associated with the oriC region in a DnaA-dependent manner and limited the amount of DnaA at oriC. In vitro, purified YabA altered binding of DnaA to DNA by inhibiting cooperativity. Although previously undescribed, proteins that directly inhibit cooperativity may be a common mechanism for regulating replication initiation. Conditions that cause release of DnaN from the replisome, or overproduction of DnaN, caused decreased association of YabA and increased association of DnaA with oriC. This effect of DnaN, either directly or indirectly, is likely responsible, in part, for enabling initiation of a new round of replication following completion of a previous round.
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spelling mit-1721.1/741052022-09-29T12:43:13Z Control of the replication initiator DnaA by an anti-cooperativity factor Merrikh, Houra Massachusetts Institute of Technology. Department of Biology Grossman, Alan D. Merrikh, Houra Proper coordination of DNA replication with cell growth and division is critical for production of viable progeny. In bacteria, coordination of DNA replication with cell growth is generally achieved by controlling activity of the replication initiator DnaA and its access to the chromosomal origin of replication, oriC. Here we describe a previously unknown mechanism for regulation of DnaA. YabA, a negative regulator of replication initiation in Bacillus subtilis, interacts with DnaA and DnaN, the sliding (processivity) clamp of DNA polymerase. We found that in vivo, YabA associated with the oriC region in a DnaA-dependent manner and limited the amount of DnaA at oriC. In vitro, purified YabA altered binding of DnaA to DNA by inhibiting cooperativity. Although previously undescribed, proteins that directly inhibit cooperativity may be a common mechanism for regulating replication initiation. Conditions that cause release of DnaN from the replisome, or overproduction of DnaN, caused decreased association of YabA and increased association of DnaA with oriC. This effect of DnaN, either directly or indirectly, is likely responsible, in part, for enabling initiation of a new round of replication following completion of a previous round. United States. Public Health Service (grant GM41934) National Institutes of Health (U.S.) (NIH Kirschstein NRSA postdoctoral fellowship F32GM093408) 2012-10-18T19:19:24Z 2012-10-18T19:19:24Z 2011-09 Article http://purl.org/eprint/type/JournalArticle 0950-382X 1365-2958 http://hdl.handle.net/1721.1/74105 Merrikh, Houra, and Alan D. Grossman. “Control of the Replication Initiator DnaA by an Anti-cooperativity Factor.” Molecular Microbiology 82.2 (2011): 434–446. Web. https://orcid.org/0000-0002-8235-7227 en_US http://dx.doi.org/10.1111/j.1365-2958.2011.07821.x Molecular Microbiology Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf John Wiley & Sons, Inc. PMC
spellingShingle Merrikh, Houra
Control of the replication initiator DnaA by an anti-cooperativity factor
title Control of the replication initiator DnaA by an anti-cooperativity factor
title_full Control of the replication initiator DnaA by an anti-cooperativity factor
title_fullStr Control of the replication initiator DnaA by an anti-cooperativity factor
title_full_unstemmed Control of the replication initiator DnaA by an anti-cooperativity factor
title_short Control of the replication initiator DnaA by an anti-cooperativity factor
title_sort control of the replication initiator dnaa by an anti cooperativity factor
url http://hdl.handle.net/1721.1/74105
https://orcid.org/0000-0002-8235-7227
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