Biomaterial Database

Two mechanisms produce mutation hotspots at DNA breaks in Escherichia coli. 2012

Chandan Shee, and Janet L Gibson, and Susan M Rosenberg

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Mutation hotspots and showers occur across phylogeny and profoundly influence genome evolution, yet the mechanisms that produce hotspots remain obscure. We report that DNA double-strand breaks (DSBs) provoke mutation hotspots via stress-induced mutation in Escherichia coli. With tet reporters placed 2 kb to 2 Mb (half the genome) away from an I-SceI site, RpoS/DinB-dependent mutations occur maximally within the first 2 kb and decrease logarithmically to ∼60 kb. A weak mutation tail extends to 1 Mb. Hotspotting occurs independently of I-site/tet-reporter-pair position in the genome, upstream and downstream in the replication path. RecD, which allows RecBCD DSB-exonuclease activity, is required for strong local but not long-distance hotspotting, indicating that double-strand resection and gap-filling synthesis underlie local hotspotting, and newly illuminating DSB resection in vivo. Hotspotting near DSBs opens the possibility that specific genomic regions could be targeted for mutagenesis, and could also promote concerted evolution (coincident mutations) within genes/gene clusters, an important issue in the evolution of protein functions.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D004926	Escherichia coli	A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.	Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D001426	Bacterial Proteins	Proteins found in any species of bacterium.	Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D012808	Sigma Factor	A protein which is a subunit of RNA polymerase. It effects initiation of specific RNA chains from DNA.	Sigma Element,Sigma Initiation Factor,Sigma Subunit,Minor Sigma Factor,RNA Polymerase Sigma Factor H,Factor, Sigma,Factor, Sigma Initiation,Initiation Factor, Sigma,Sigma Factor, Minor,Subunit, Sigma
D043211	Exodeoxyribonuclease V	An ATP-dependent exodeoxyribonuclease that cleaves in either the 5'- to 3'- or the 3'- to 5'-direction to yield 5'-phosphooligonucleotides. It is primarily found in BACTERIA.	ATP-Dependent DNase,Exodeoxyribonuclease V, alpha Chain,Exodeoxyribonuclease V, beta Chain,Exodeoxyribonuclease V, gamma Chain,Exonuclease V,RecBC DNase,RecBC Deoxyribonuclease,RecBCD Enzyme,ATP Dependent DNase,Deoxyribonuclease, RecBC
D053903	DNA Breaks, Double-Stranded	Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.	Double-Stranded DNA Breaks,Double-Strand DNA Breaks,Double-Stranded DNA Break,Break, Double-Strand DNA,Break, Double-Stranded DNA,Breaks, Double-Strand DNA,Breaks, Double-Stranded DNA,DNA Break, Double-Strand,DNA Break, Double-Stranded,DNA Breaks, Double Stranded,DNA Breaks, Double-Strand,Double Strand DNA Breaks,Double Stranded DNA Break,Double Stranded DNA Breaks,Double-Strand DNA Break
D017930	Genes, Reporter	Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.	Reporter Genes,Gene, Reporter,Reporter Gene
D029968	Escherichia coli Proteins	Proteins obtained from ESCHERICHIA COLI.	E coli Proteins