DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader

DSpace/Manakin Repository

DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader

Citable link to this page

 

 
Title: DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader
Author: Rock, Jeremy M.; Lang, Ulla F.; Chase, Michael R.; Ford, Christopher B.; Gerrick, Elias R.; Gawande, Richa; Coscolla, Mireia; Gagneux, Sebastien; Fortune, Sarah M.; Lamers, Meindert H.

Note: Order does not necessarily reflect citation order of authors.

Citation: Rock, Jeremy M., Ulla F. Lang, Michael R. Chase, Christopher B. Ford, Elias R. Gerrick, Richa Gawande, Mireia Coscolla, Sebastien Gagneux, Sarah M. Fortune, and Meindert H. Lamers. 2015. “DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader.” Nature genetics 47 (6): 677-681. doi:10.1038/ng.3269. http://dx.doi.org/10.1038/ng.3269.
Full Text & Related Files:
Abstract: The DNA replication machinery is an important target for antibiotic development for increasingly drug resistant bacteria including Mycobacterium tuberculosis1. While blocking DNA replication leads to cell death, disrupting the processes used to ensure replication fidelity can accelerate mutation and the evolution of drug resistance. In E. coli, the proofreading subunit of the replisome, the ε-exonuclease, is essential for high fidelity DNA replication2; however, we find that it is completely dispensable in M. tuberculosis. Rather, the mycobacterial replicative polymerase, DnaE1, encodes a novel editing function that proofreads DNA replication, mediated by an intrinsic 3′-5′ exonuclease activity within its PHP domain. Inactivation of the DnaE1 PHP domain increases the mutation rate by greater than 3,000 fold. Moreover, phylogenetic analysis of DNA replication proofreading in the bacterial kingdom suggests that E. coli is a phylogenetic outlier and that PHP-domain mediated proofreading is widely conserved and indeed may be the ancestral prokaryotic proofreader.
Published Version: doi:10.1038/ng.3269
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449270/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993678
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters