A Bacterial Toxin Inhibits DNA Replication Elongation through a Direct Interaction with the β Sliding Clamp
Name
Laub_A bacterial toxin.pdf
Size
4.58 MB
Format
Adobe PDF
Checksum (MD5)
b2793c994ed0a3c3e8c559df9c6a79df
Author(s)
Aakre, Christopher David
Phung, Tuyen N.
Huang, David
Laub, Michael T
Date Issued
November 2013
Journal
Molecular Cell
Publisher
Elsevier
Citation
Aakre, Christopher D. et al. “A Bacterial Toxin Inhibits DNA Replication Elongation through a Direct Interaction with the β Sliding Clamp.” Molecular Cell 52.5 (2013): 617–628.
Version
Author's final manuscript
Abstract
Toxin-antitoxin (TA) systems are ubiquitous on bacterial chromosomes, yet the mechanisms regulating their activity and the molecular targets of toxins remain incompletely defined. Here, we identify SocAB, an atypical TA system in Caulobacter crescentus. Unlike canonical TA systems, the toxin SocB is unstable and constitutively degraded by the protease ClpXP; this degradation requires the antitoxin, SocA, as a proteolytic adaptor. We find that the toxin, SocB, blocks replication elongation through an interaction with the sliding clamp, driving replication fork collapse. Mutations that suppress SocB toxicity map to either the hydrophobic cleft on the clamp that binds DNA polymerase III or a clamp-binding motif in SocB. Our findings suggest that SocB disrupts replication by outcompeting other clamp-binding proteins. Collectively, our results expand the diversity of mechanisms employed by TA systems to regulate toxin activity and inhibit bacterial growth, and they suggest that inhibiting clamp function may be a generalizable antibacterial strategy.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.molcel.2013.10.014
