A new role for Escherichia coli Dam DNA methylase in prevention of aberrant chromosomal replication.
Alleles
Bacterial Proteins
/ metabolism
Chromosome Aberrations
Chromosomes
/ genetics
DNA
/ metabolism
DNA Repair
DNA Replication
DNA, Bacterial
/ metabolism
DNA-Binding Proteins
/ metabolism
Escherichia coli
/ enzymology
Escherichia coli Proteins
/ metabolism
Gene Dosage
Gene Expression Regulation, Bacterial
Mutation
Phenotype
Phleomycins
/ chemistry
Recombination, Genetic
Sequence Analysis, DNA
Site-Specific DNA-Methyltransferase (Adenine-Specific)
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
20 06 2019
20 06 2019
Historique:
accepted:
26
03
2019
revised:
20
03
2019
received:
14
01
2019
pubmed:
9
4
2019
medline:
4
12
2019
entrez:
9
4
2019
Statut:
ppublish
Résumé
The Dam DNA methylase of Escherichia coli is required for methyl-directed mismatch repair, regulation of chromosomal DNA replication initiation from oriC (which is DnaA-dependent), and regulation of gene expression. Here, we show that Dam suppresses aberrant oriC-independent chromosomal replication (also called constitutive stable DNA replication, or cSDR). Dam deficiency conferred cSDR and, in presence of additional mutations (Δtus, rpoB*35) that facilitate retrograde replication fork progression, rescued the lethality of ΔdnaA mutants. The DinG helicase was required for rescue of ΔdnaA inviability during cSDR. Viability of ΔdnaA dam derivatives was dependent on the mismatch repair proteins, since such viability was lost upon introduction of deletions in mutS, mutH or mutL; thus generation of double strand ends (DSEs) by MutHLS action appears to be required for cSDR in the dam mutant. On the other hand, another DSE-generating agent phleomycin was unable to rescue ΔdnaA lethality in dam+ derivatives (mutS+ or ΔmutS), but it could do so in the dam ΔmutS strain. These results point to a second role for Dam deficiency in cSDR. We propose that in Dam-deficient strains, there is an increased likelihood of reverse replication restart (towards oriC) following recombinational repair of DSEs on the chromosome.
Identifiants
pubmed: 30957852
pii: 5430841
doi: 10.1093/nar/gkz242
pmc: PMC6582345
doi:
Substances chimiques
Bacterial Proteins
0
DNA, Bacterial
0
DNA-Binding Proteins
0
Escherichia coli Proteins
0
Phleomycins
0
DNA
9007-49-2
Dam methyltransferase
EC 2.1.1.72
Site-Specific DNA-Methyltransferase (Adenine-Specific)
EC 2.1.1.72
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5698-5711Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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