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Structures of Escherichia coli DNA adenine methyltransferase (Dam) in complex with a non-GATC sequence: Potential implications for methylation-independent transcriptional repression

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gkv251· OSTI ID:1223724
 [1];  [1];  [2];  [1]
  1. Emory Univ. School of Medicine, Atlanta, GA (United States)
  2. The Univ. of Toledo College of Medicine and Life Sciences, Toledo, OH (United States)
DNA adenine methyltransferase (Dam) is widespread and conserved among the γ-proteobacteria. Methylation of the Ade in GATC sequences regulates diverse bacterial cell functions, including gene expression, mismatch repair and chromosome replication. Dam also controls virulence in many pathogenic Gram-negative bacteria. An unexplained and perplexing observation about Escherichia coli Dam (EcoDam) is that there is no obvious relationship between the genes that are transcriptionally responsive to Dam and the promoter-proximal presence of GATC sequences. Here, we demonstrate that EcoDam interacts with a 5-base pair non-cognate sequence distinct from GATC. The crystal structure of a non-cognate complex allowed us to identify a DNA binding element, GTYTA/TARAC (where Y = C/T and R = A/G). This element immediately flanks GATC sites in some Dam-regulated promoters, including the Pap operon which specifies pyelonephritis-associated pili. In addition, Dam interacts with near-cognate GATC sequences (i.e. 3/4-site ATC and GAT). All together, these results imply that Dam, in addition to being responsible for GATC methylation, could also function as a methylation-independent transcriptional repressor.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Grant/Contract Number:
AC02-06CH11357; W-31109-ENG-38
OSTI ID:
1223724
Alternate ID(s):
OSTI ID: 1247332
Journal Information:
Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 8 Vol. 43; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (2)

A role for the bacterial GATC methylome in antibiotic stress survival journal March 2016
The cell cycle-regulated DNA adenine methyltransferase CcrM opens a bubble at its DNA recognition site journal October 2019

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