title: Diverse effects of naturally occurring base lesions on the structure and stability of the human telomere DNA quadruplex.
abstract: Various base lesions continuously form in cellular nucleic acids and the unrepaired lesions are promutagenic and procarcinogenic. Though natural base lesions have been extensively studied in double-stranded DNA models, these studies are only less than a decade old for non-canonical DNA models, such as quadruplexes. Here we present a report on the effects of three frequently occurring natural lesions that can form in the TTA loops on the structure of the human telomere quadruplex d[AG3(TTAG3)3]. We compared the effect of the abasic site and 8-oxoadenine replacing adenine and 5-hydroxymethyluracil substituting for thymine. The results showed that the three lesions impacted the stability and quadruplex folding in markedly different ways. The effects depended on the type of lesion and the position in the sequence. Analogous lesions of guanine in the G-tetrads extensively destabilized the quadruplex and the effects depended more on the position than on the type of lesion. The distinct effects of the loop substitutions as well as comparison of the modifications of the loops and the quadruplex tetrads are discussed in this communication.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic; Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 61137 Brno, Czech Republic; CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Konvalinová
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic; Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 61137 Brno, Czech Republic; CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Dvořáková
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic; CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Renčiuk
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic; CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Klára
authors.initials: K
authors.lastname: Bednářová
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic; CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Kejnovská
authors.affiliation: CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Trantírek
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic; CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. Electronic address: mifi@ibp.cz.
authors.forename: Michaela
authors.initials: M
authors.lastname: Vorlíčková
authors.affiliation: Rimstone Laboratory, RLI, 3618 Promontory Pl, Carlsbad, CA 92010, USA. Electronic address: jans@rimstonelab.com.
authors.forename: Janos
authors.initials: J
authors.lastname: Sagi
mesh_terms: D002942:Circular Dichroism; D004249:DNA Damage / Q000235:genetics*; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D016615:Telomere / Q000737:chemistry* / Q000235:genetics
keywords: Base modification; Circular dichroism spectroscopy; DNA secondary structure; Guanine quadruplex; Oxidative damage