The effect of single nucleotide polymorphisms in G-rich regions of high-risk human papillomaviruses on structural diversity of DNA.
Infection with high-risk human papillomaviruses (HPVs) can lead to development of cancer of the head and neck and anogenital regions. G-rich sequences found in genomes of high-risk HPVs can fold into non-canonical secondary structures that could serve as 3D motifs distinct from double-stranded DNA and present recognition sites for ligands and opportunity for gene expression modulation.



Combination of UV, CD and NMR spectroscopy and PAGE electrophoresis were used as they offer complementary insights into structural changes of G-rich oligonucleotides.



G-rich region of HPV16 is shown to preferentially form hairpin structures, while regions of HPV18, HPV52 and HPV58 fold into four-stranded DNA structures called G-quadruplexes. Single nucleotide polymorphisms found in G-rich sequences have been found to promote formation of hairpin structures of HPV16 and have affected number of species formed in G-rich region of HPV52, whereas they have exhibited minimal effect on the formation of HPV18 and HPV58 G-quadruplex structures. These structural changes were reflected in differences in apparent thermal stabilities.



Potential of G-rich sequences as drug targets was evaluated based on the results of the current study. HPV16 and HPV18 are considered less appropriate targets due to several single nucleotide polymorphisms and low stability, respectively. On the other hand, HPV52 and HPV58 could be used for small-molecule mediated stabilization.



G-rich sequences occurring in high-risk HPVs can fold into hairpin and G-quadruplex structures that could be potentially utilized as drug targets. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.
Slovenian NMR Institute, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
Maja
M
Marušič
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Zaloška 4, SI-1000 Ljubljana, Slovenia.
Lea
L
Hošnjak
Department of Biochemistry, Institute of Chemistry, Faculty of Sciences, P. J. Safarik University, 04001 Kosice, Slovakia.
Petra
P
Krafčikova
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Zaloška 4, SI-1000 Ljubljana, Slovenia.
Mario
M
Poljak
Department of Biochemistry, Institute of Chemistry, Faculty of Sciences, P. J. Safarik University, 04001 Kosice, Slovakia.
Viktor
V
Viglasky
Slovenian NMR Institute, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia; EN-FIST Center of Excellence, SI-1000 Ljubljana, Slovenia; Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia. Electronic address: janez.plavec@ki.si.
Janez
J
Plavec
D000998:Antiviral Agents / Q000494:pharmacology; D002942:Circular Dichroism; D004279:DNA, Viral / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics*; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D054856:G-Quadruplexes; D005838:Genotype; D006147:Guanine / Q000737:chemistry*; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D055029:Inverted Repeat Sequences; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009691:Nucleic Acid Denaturation; D027383:Papillomaviridae / Q000187:drug effects / Q000235:genetics*; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000821:virology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013696:Temperature
D000998:Antiviral Agents; D004279:DNA, Viral; D006147:Guanine
G-quadruplex; HPV; Hairpin; NMR; Nucleic acids structures; Single nucleotide polymorphism