Diverse effects of naturally occurring base lesions on the structure and stability of the human telomere DNA quadruplex

0455955 - BFÚ 2016 RIV FR eng J - Journal Article
Konvalinová, Helena - Dvořáková, Zuzana - Renčiuk, Daniel - Bednářová, Klára - Kejnovská, Iva - Trantírek, L. - Vorlíčková, Michaela - Sagi, J.
Diverse effects of naturally occurring base lesions on the structure and stability of the human telomere DNA quadruplex.
Biochimie. Roč. 118, NOV 2015 (2015), s. 15-25. ISSN 0300-9084. E-ISSN 1638-6183
R&D Projects: GA ČR(CZ) GAP205/12/0466; GA ČR(CZ) GA13-28310S; GA ČR(CZ) GA15-06785S
Institutional support: RVO:68081707
Keywords : DNA secondary structure * Circular dichroism spectroscopy * Guanine quadruplex
Subject RIV: BO - Biophysics
Impact factor: 3.017, year: 2015

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[AG(3)(TTAG(3))(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.
Permanent Link: http://hdl.handle.net/11104/0256554