TY - JOUR
T1 - Genome-wide study predicts promoter-G4 DNA motifs regulate selective functions in bacteria
T2 - Radioresistance of D. radiodurans involves G4 DNA-mediated regulation
AU - Beaume, Nicolas
AU - Pathak, Rajiv
AU - Yadav, Vinod Kumar
AU - Kota, Swathi
AU - Misra, Hari S.
AU - Gautam, Hemant K.
AU - Chowdhury, Shantanu
N1 - Funding Information:
Council of Scientific & Industrial Research (postdoctoral fellowship for foreign scholars (to N.B.); financial assistant [OLP 6101 to H.K.G.]; Department of Science and Technology (Swarnajayanti Fellowship for research grant (to S.C.); University Grants Commission, India (Junior Research Fellowship to R.P.). Funding for open access charge: Swarnajayanti Fellowship by Department of Science and Technology.
PY - 2013/1
Y1 - 2013/1
N2 - A remarkable number of guanine-rich sequences with potential to adopt non-canonical secondary structures called G-quadruplexes (or G4 DNA) are found within gene promoters. Despite growing interest, regulatory role of quadruplex DNA motifs in intrinsic cellular function remains poorly understood. Herein, we asked whether occurrence of potential G4 (PG4) DNA in promoters is associated with specific function(s) in bacteria. Using a normalized promoter-PG4-content (PG4P) index we analysed >60 000 promoters in 19 well-annotated species for (a) function class(es) and (b) gene(s) with enriched PG4 P. Unexpectedly, PG4-associated functional classes were organism specific, suggesting that PG4 motifs may impart specific function to organisms. As a case study, we analysed radioresistance. Interestingly, unsupervised clustering using PG4P of 21 genes, crucial for radioresistance, grouped three radioresistant microorganisms including Deinococcus radiodurans. Based on these predictions we tested and found that in presence of nanomolar amounts of the intracellular quadruplex-binding ligand N-methyl mesoporphyrin (NMM), radioresistance of D. radiodurans was attenuated by ∼60%. In addition, important components of the RecF recombinational repair pathway recA, recF, recO, recR and recQ genes were found to harbour promoter-PG4 motifs and were also down-regulated in presence of NMM. Together these results provide first evidence that radioresistance may involve G4 DNA-mediated regulation and support the rationale that promoter-PG4s influence selective functions.
AB - A remarkable number of guanine-rich sequences with potential to adopt non-canonical secondary structures called G-quadruplexes (or G4 DNA) are found within gene promoters. Despite growing interest, regulatory role of quadruplex DNA motifs in intrinsic cellular function remains poorly understood. Herein, we asked whether occurrence of potential G4 (PG4) DNA in promoters is associated with specific function(s) in bacteria. Using a normalized promoter-PG4-content (PG4P) index we analysed >60 000 promoters in 19 well-annotated species for (a) function class(es) and (b) gene(s) with enriched PG4 P. Unexpectedly, PG4-associated functional classes were organism specific, suggesting that PG4 motifs may impart specific function to organisms. As a case study, we analysed radioresistance. Interestingly, unsupervised clustering using PG4P of 21 genes, crucial for radioresistance, grouped three radioresistant microorganisms including Deinococcus radiodurans. Based on these predictions we tested and found that in presence of nanomolar amounts of the intracellular quadruplex-binding ligand N-methyl mesoporphyrin (NMM), radioresistance of D. radiodurans was attenuated by ∼60%. In addition, important components of the RecF recombinational repair pathway recA, recF, recO, recR and recQ genes were found to harbour promoter-PG4 motifs and were also down-regulated in presence of NMM. Together these results provide first evidence that radioresistance may involve G4 DNA-mediated regulation and support the rationale that promoter-PG4s influence selective functions.
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U2 - 10.1093/nar/gks1071
DO - 10.1093/nar/gks1071
M3 - Article
C2 - 23161683
AN - SCOPUS:84871728994
SN - 0305-1048
VL - 41
SP - 76
EP - 89
JO - Nucleic acids research
JF - Nucleic acids research
IS - 1
ER -