Control of the replication initiator DnaA by an anti-cooperativity factor
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Grossman_Control of.pdf
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678.86 KB
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7851046165d345ca4eeb24a94058a50e
Author(s)
Merrikh, Houra
Date Issued
September 2011
Journal
Molecular Microbiology
Publisher
John Wiley & Sons, Inc.
Citation
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.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1111/j.1365-2958.2011.07821.x
