A Bacterial Chromosome Structuring Protein Binds Overtwisted DNA to Stimulate Type II Topoisomerases and Enable DNA Replication
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nihms-1504257.pdf
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Accepted version
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Author(s)
Guo, Monica S
Haakonsen, Diane Laure
Zeng, Wenjie
Schumacher, Maria A.
Laub, Michael T
Date Issued
September 2018
Journal
Cell
Publisher
Elsevier BV
Citation
Guo, Monica S. et al. "A bacterial chromosome structuring protein binds overtwisted DNA to stimulate type II topoisomerases and enable DNA replication" Cell 175, 2 (October 2018): P583-597.e23 © 2018 Elsevier Inc.
Version
Author's final manuscript
Abstract
When DNA is unwound during replication, it becomes overtwisted and forms positive supercoils in front of the translocating DNA polymerase. Unless removed or dissipated, this superhelical tension can impede replication elongation. Topoisomerases, including gyrase and topoisomerase IV in bacteria, are required to relax positive supercoils ahead of DNA polymerase but may not be sufficient for replication. Here, we find that GapR, a chromosome structuring protein in Caulobacter crescentus, is required to complete DNA replication. GapR associates in vivo with positively supercoiled chromosomal DNA, and our biochemical and structural studies demonstrate that GapR forms a dimer-of-dimers that fully encircles overtwisted DNA. Further, we show that GapR stimulates gyrase and topo IV to relax positive supercoils, thereby enabling DNA replication. Analogous chromosome structuring proteins that locate to the overtwisted DNA in front of replication forks may be present in other organisms, similarly helping to recruit and stimulate topoisomerases during DNA replication. A bacterial protein that specifically recognizes and encircles overtwisted DNA is required to stimulate the activity of type II topoisomerases and enable DNA replication.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2018.08.029
