i
DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader
-
6 2015
-
-
Source: Nat Genet. 47(6):677-681
[PDF-601.77 KB]
Details:
-
Alternative Title:Nat Genet
-
Personal Author:
-
Description:The DNA replication machinery is an important target for antibiotic development in increasingly drug-resistant bacteria, including Mycobacterium tuberculosis. Although 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 Escherichia coli, the proofreading subunit of the replisome, the ɛ exonuclease, is essential for high-fidelity DNA replication; however, we find that the corresponding subunit is completely dispensable in M. tuberculosis. Rather, the mycobacterial replicative polymerase DnaE1 itself encodes an 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 more 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.
-
Subjects:
-
Source:
-
Pubmed ID:25894501
-
Pubmed Central ID:PMC4449270
-
Document Type:
-
Funding:
-
Collection(s):
-
Main Document Checksum:
-
Download URL:
-
File Type:
Supporting Files
-
pdf 
pdf 
pdf 
xlsx 
xml 
gif 
jpeg 
gif 
jpeg 
gif 
pdf 
jpeg 
gif 
jpeg 
xls 
xlsx 
xlsx 
pdf 
pdf 
pdf 
pdf
