Ecological Factors that Induce Mutagenic DNA Repair or Modulate NGE Responses

Ecological Factor and NGE Effect

Affected Organism

References

Growth conditions and cellular differentiation

Stationary phase mutagenesis regulated by ComA and ComK

B. subtilis

(Sung and Yasbin 2002)

Anaerobic growth enhances point mutations, produces different spectrum

E. coli

(Shewaramani, Finn et al. 2017)

Aging colonies, mutational hotspots, retromutation (8-oxo-guanosine, formed exclusively on the transcribed strand)

E. coli

(Sekowska, Wendel et al. 2016) (Saint-Ruf, Garfa-Traore et al. 2014)

Nutrient-dependent mutability

E. coli mutator strains

(Tsuru, Ishizawa et al. 2015) (Ishizawa, Ying et al. 2015)

Adaptive selection-induced retromutation (damage only to transcribed DNA strand)

E. coli

(Morreall, Kim et al. 2015)

Cystic Fibrosis lung growth induces hypermutability

P. aeruginosa

(Rodriguez-Rojas, Oliver et al. 2012)

Phosphorus/carbon limitation increase point mutations, iron/oxygen/carbon limitation increase IS150 insertions, phosphorus limitation increases indels

E. coli

(Maharjan and Ferenci 2017) (Maharjan and Ferenci 2015)

Adenine starvation stimulates Ty1 retrotransposition

Yeast Saccharomyces cerevisaea

(Servant, Pinson et al. 2012)

APOBEC kataegis on actively transcribed loci

Yeast Saccharomyces cerevisaea

(Lada, Kliver et al. 2015)

Glucose- or phosphate-limited growth produced frequent genomic amplifications, rearrangements and novel retrotransposition.

Yeast Saccharomyces cerevisiae

(Gresham, Desai et al. 2008)

“Starvation leads to genome restructuring. By contrast, the frequency of point mutations is less than 2-fold greater.”

Yeast Saccharomyces cerevisiae

(Kroll, Coyle et al. 2013)

Nitrogen starvation increases copy number variations (CNVs)

Yeast Saccharomyces cerevisiae

(Hong and Gresham 2014)

Domestication leads to increase in repetitive DNA and retrotransposons

Maize

(Liu, Zheng et al. 2017)

Early embryogenesis activates mPing DNA transposition

Rice

(Teramoto, Tsukiyama et al. 2014)

Plant regeneration activates chromovirus LORE1 (ERV) retrotransposition

Model legume Lotus japonicus

(Fukai, Umehara et al. 2010)

Neural differentiation activates L1 retrotransposition.

Rodents, humans

(Richardson, Morell et al. 2014)

Aging induces retrotransposition (effect counter-acted by calorie restriction)

Mouse germline and somatic tissue

(De Cecco, Criscione et al. 2013)

Early embryonic development displays a mutator state for copy number variation (CNV) of genomic duplications

Humans

(Liu, Yuan et al. 2017)

Abiotic stresses

UV irradiation stimulates hypermutation

Pseudomonas aeruginosa

(Weigand and Sundin 2012)

Oxidative stress induce DNA transposon non-allelic homolgous recombination (NAHR)

Burkholderia cenocepacia

(Drevinek, Baldwin et al. 2010)

Cis-platin treatment hypermutation

Yeast mutants, rad1, rad2 S. cerevisaea

(Segovia, Shen et al. 2017)

Copper induces expansion and contraction of CUP1 arrays encoding copper-binding protein (copy number variation, CNV)

Budding yeast Saccharomyces cerevisaea

(Hull, Cruz et al. 2017)

Heat shock, oxidative and copper sulphate stresses activate LTR-retrotransposons Pyret and MAGGY, DNA transposons Pot3, MINE, Mg-SINE, Grasshopper and MGLR3

Fungal pathogen Magnaporthe oryzae

(Chadha and Sharma 2014)

Mild heat stress and UV activate mariner-Mos1 transposition

Drosophila simulans

(Jardim, Schuch et al. 2015)

Sun exposure increases somatic mutations

Skin fibroblasts

(Saini, Roberts et al. 2016) (Abyzov, Tomasini et al. 2017)

Uranium induces alternative NHEJ DSB repair processes

Embryonic zebrafish cells

(Pereira, Camilleri et al. 2012)

“Two mechanisms … of cadmium mutagenicity: (i) induction of reactive oxygen species (ROS); and (ii) inhibition of DNA repair.”

Various mammalian experimental systems

(Filipic, Fatur et al. 2006)

Arsenic, vanadium, iron induce VL30 retrotransposition

Mouse NIH3T3 cells

(Markopoulos, Noutsopoulos et al. 2013) (Noutsopoulos, Markopoulos et al. 2007) (Konisti, Mantziou et al. 2012)

“Environmental stressors, as ionizing radiation (terrestrial, space, and UV-radiation), air pollution (including particulate matter [PM]-derived and gaseous), persistent organic pollutants, and metals” activate mobile DNA elements.

Humans

(Miousse, Chalbot et al. 2015)

Mercury induces LINE1 retrotransposition

Human neuroblastoma cell line

(Habibi, Shokrgozar et al. 2014)

Heavy metals affect DSB repair: low doses of NiCl2 favored homologous recombination (HR) and single strand annealing (SSA), which were inhibited by higher NiCl2 doses.

Human U2OS osteosarcoma cell lines

(Morales, Derbes et al. 2016)

Low doses of NiCl2 and CdCl2 contributed to an increase in mutagenic deletions by Alu-Alu NAHR…cells exposed to arsenic trioxide preferentially repaired using the "error prone" non-homologous end joining (alt-NHEJ) while inhibiting repair by HR.

Human HEK 293 cells

(Morales, Derbes et al. 2016)

Etomoxir, WY-14643, and salicylamide (genotoxic drugs), Aluminum, low-level As2O3 induce LINE1 retrotransposition; copper treatment downregulated L1 retrotransposition.

Human HepG2 cells

(Terasaki, Goodier et al. 2013) (Karimi, Madjd et al. 2014) (Karimi, Madjd et al. 2014)

Exposure to cadmium chloride and cadmium diacetate inhibits NHEJ and activates MRE11-dependent repair

Human endothelial cells

(Viau, Gastaldo et al. 2008)

Heat stress activates ONSEN, COPIA retrotransposition

Brassicaceae

(Ito, Yoshida et al. 2013) (Ito, Kim et al. 2016; Masuta, Nozawa et al. 2016; Pietzenuk, Markus et al. 2016)

Heat stress activates ONSEN retrotransposition

Arabidopsis

(Matsunaga, Ohama et al. 2015) (Cavrak, Lettner et al. 2014)

Climate affects DNA transposon and retrotransposon activity

Arabidopsis

(Quadrana, Bortolini Silveira et al. 2016) (Ito and Kakutani 2014)

Cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells

Trinucleotide repeat mutagenesis in humans

(Chatterjee, Lin et al. 2015) (Chatterjee, Lin et al. 2016)

Microsatellite mutation rate is significantly greater at 26°C than at 18°C

C. elegans

(Matsuba, Ostrow et al. 2013)

Hyper salinity, stressed lineages accumulate ∼100% more mutations, and these mutations exhibit a distinctive molecular mutational spectrum (specific increases in relative frequency of transversion and insertion/deletion {indel} mutations).

A. thaliana

(Jiang, Mithani et al. 2014)

Nitric oxide modulator, sodium nitroprusside induces Tos17 LTR retrotransposition.

Rice

(Ou, Zhuang et al. 2015)

Laser irradiation stimulates DNA methylation changes and mPing DNA transposition

Rice

(Li, Xia et al. 2017)

Fungicides boscalid (respiration inhibitor), iprodione (unclear mode of action), thiophanate methyl (inhibition of microtubulin synthesis) and azoxystrobin and pyraclostrobin (quinone outside inhibitors) raised mutation rates 1.7- to 60-fold compared to neutral conditions. 

Plant pathogen Sclerotinia sclerotiorum

(Amaradasa and Everhart 2016)

Biotic stresses and biomolecules

Ethanol stress induces transient hypermutator state

E. coli

(Swings, Van den Bergh et al. 2017)

Food additive sepiolite stimulates antibiotic resistance plasmid transfer

E. coli, S. Typhimurium, M. smegmatis, and P. aeruginosa

(Rodriguez-Beltran, Rodriguez-Rojas et al. 2013)

Joint action of LL-37 (antimicrobial peptide) and free iron induces mutagenesis

P. aeruginosa

(Rodriguez-Rojas, Makarova et al. 2014)

Antibiotics induce SOS response and conjugal DNA transfer

V. cholera

(Baharoglu, Bikard et al. 2010; Baharoglu and Mazel 2011; Baharoglu, Krin et al. 2013; Gutierrez, Laureti et al. 2013)

Fluoroquinolone and norfloxacin antibiotics induced point mutations, IS1 non-allelic homologous recombination (NAHR) deletions, IS5 NAHR duplications (but not transpositions)

E. coli

(Long, Miller et al. 2016)

Beta-lactam antibiotics induced RpoS-dependent mutagenesis

E. coli

(Gutierrez, Laureti et al. 2013)

Ciprofloxacin enhanced mutability

E. coli

 (Jee, Rasouly et al. 2016) (Song, Goff et al. 2016) (Kohanski, DePristo et al. 2010)

Subinhibitory ciprofloxacin, SOS response

Pseudomonas aeruginosa

(Valencia, Esposito et al. 2017; Zaborskyte, Andersen et al. 2017)

Subinhibitory concentrations of ciprofloxacin and vancomycin activate IS256 transposition, induce SOS response; also chloramphenicol and spectinomycin

Staphylococcus aureus

(Nagel, Reuter et al. 2011; Schreiber, Szekat et al. 2013)

Antibiotic selection induces genomic duplications

E. coli

(Laehnemann, Pena-Miller et al. 2014)

Tigecycline induces hypermutation

Acinetobacter baumannii

(Hammerstrom, Beabout et al. 2015)

Cationic antimicrobial peptide human cathelicidin LL-37 induces mutagenesis in CF lungs

P. aeruginosa

(Limoli, Rockel et al. 2014)

Canavanine proteotoxic stress induces mutagenesis

Yeast S. cerevisaea

(Shor, Fox et al. 2013)

Cyclo(phenylalanine-proline) produced by animals, plants, bacteria and fungi... such as Lactobacillus reuteri, Streptomyces sp. AMLK‐335, Vibrio vulnificus, V. cholera, Pseudomonas aeruginosa and P. putida; induces phosphorylation of H2AX (S139) through ATM-CHK2 activation as well as DNA double strand breaks. Gene expression analysis revealed that cyclo(phenylalanine-proline) repressed a subset of genes related to reactive oxygen species (ROS) scavenging.

Human INT‐407, U2OS and Huh7 cells

(Lee, Jeong et al. 2015)

Chlamydia trachomatis infection produces

8-oxo-dG, DSBs

Human cervical, ovarian cells

(Chumduri, Gurumurthy et al. 2016)

N. gonorrhea gonococcal infection causes DNA strand breaks, abolished expression of p53 and increased in expression of cyclin-dependent kinase inhibitors p21 and p27

Human non-tumor vaginal VK2/E6E7 cells

(Vielfort, Soderholm et al. 2013)

H.  pylori infection is mutagenic/carcinogenic; CagA, VacA, γGT, urease, NapA proteins induce 8-oxo-G, 8-oxo-dG, AP sites, and DSBs in host DNA, mutagenic DNA damage response

Human gastric cells

(Touati 2010) (Hanada, Uchida et al. 2014) (Toller, Neelsen et al. 2011) (Chumduri, Gurumurthy et al. 2016)

 

Helicobacter pylori impairs DNA mismatch repair

Human gastric epithelial cells

(Kim, Tao et al. 2002)

Haemophilus ducreyi CDT (HdCDT) DNAse genotoxin induces phosphorylation of the histone H2AX as early as 1 h after intoxication and re-localization of the DNA repair complex Mre11 in HeLa cells with kinetics similar to those observed upon ionizing radiation.

HeLa cells

(Li, Sharipo et al. 2002)

Campylobacter jejuni, Haemophilus ducreyi, Actinobacillus actinomycetemcomitans, Shigella dysenteriae, Helicobacter cinaedi, Helicobacter hepaticus, Salmonella species CDT and CDT-like typhoid toxins induce DSBs and SSBs

Human gastric cells

(Chumduri, Gurumurthy et al. 2016)

 

Shigella strains, E. coli strains - Shiga toxin (RNA N-glycosidase) produces apurinic sites, SSBs, DSBs

Human cells

(Chumduri, Gurumurthy et al. 2016)

 

Chlamydia trachomatis infection induces DNA DSB damage and inhibits recruitment of the DDR proteins pATM and 53BP1 to damage sites

Human cells

(Chumduri, Gurumurthy et al. 2013)

E. coli harboring “pks” genomic island that codes for polyketide-peptide genotoxin, Colibactin {DNA cross-linking agent}.…pks(+) E. coli induce transient DNA damage response, incomplete DNA repair, anaphase bridges and chromosome aberrations from breakage-fusion-bridge cycles and chromosomal instability. Exposed cells exhibited a significant increase in 6-thioguanine–resistant (hprt mutant) colonies and a significant increase of tk mutants selected with trifluorothymidine.

Cultured mouse intestinal loop epithelial cells

(Cuevas-Ramos, Petit et al. 2010) (Vizcaino and Crawford 2015)

Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Citrobacter koseri colibactin genotoxin induces genome instability

Human colorectal cells

(Chumduri, Gurumurthy et al. 2016)

Neisseria gonorrhoeae, Neisseria meningitides restriction endonuclease produces 8-oxo-G, DSBs

Human prostate cells

(Chumduri, Gurumurthy et al. 2016)

E. coli depletes host cell DNA mismatch repair (MMR) proteins

Human colonic cell lines

(Maddocks, Scanlon et al. 2013)

P. aeruginosa ExoS bacterial toxin is major factor involved in γH2AX induction… infection by P. aeruginosa activates the DSB repair machinery of the host cells.

Human immune or lung epithelial cells

(Elsen, Collin-Faure et al. 2013) (Wu, Huang et al. 2011)

Listeria monocytogenes induces DSBs but dampens host DSB response through degradation of MRE11 exonuclease via bacterial factor LLO (pore-forming toxin listeriolysin O)

Human HeLa (CCL-2) and Jeg-3 (HTB-36) cell lines

(Samba-Louaka, Pereira et al. 2014) (Leitao, Costa et al. 2014)

P. syringae pathovar tomato infection induces DSB formation in Arabidopsis… abundance of infection-induced DSBs reduced by salicylic acid

Arabidopsis

(Song and Bent 2014)

Attack by the oomycete pathogen Peronospora parasitica stimulates somatic recombination

Arabidopsis

(Lucht, Mauch-Mani et al. 2002)

Tobacco mosaic virus (TMV) or oilseed rape mosaic virus (ORMV) tobacco leaf infection resulted in a systemic increase in homologous recombination (HR)…a similar phenomenon occurs in Arabidopsis thaliana plants infected with ORMV.

Arabidopsis, tobacco

(Yao, Kathiria et al. 2013)

DNA damage response induced by infection with human cytomegalovirus

Human cells

(Xiaofei and Kowalik 2014)

Human T-cell lymphotropic virus 1 (HTLV-1) retrovirus infection causes genome instability and DNA damage, attenuation of BER, NER, MMR, HR, NHEJ repair pathways, generation of ROS

Human T-cells

(Ryan, Hollingworth et al. 2016)

Hepatitis C virus (HCV) infection produces ROS and NO, reduced MMR, BER and NER, modulation of ATM pathway activity

Human cells

(Ryan, Hollingworth et al. 2016)

Zika virus infection leads to P53 activation and genotoxic stress

Human neural progenitor cells

(Ghouzzi, Bianchi et al. 2016)

Bs1 Transposition detected in maize lines following barley stripe mosaic virus infection

Zea mays

(Grandbastien 2015)

Physiological stress, induced by climate change or invasion of new habitats, disrupts epigenetic regulation and activates mobile DNA elements

Diverse organisms

(Garcia Guerreiro, Chavez-Sandoval et al. 2008) (Garcia Guerreiro 2012) (Negi, Rai et al. 2016)

 

 

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