Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00476265" target="_blank" >RIV/68081707:_____/17:00476265 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/17:00095078

Result on the web

<a href="http://dx.doi.org/10.1093/nar/gkx191" target="_blank" >http://dx.doi.org/10.1093/nar/gkx191</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkx191" target="_blank" >10.1093/nar/gkx191</a>

Result language

angličtina

Original language name

Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes

Original language description

Ionizing radiation produces clustered damage to DNA which is difficult to repair and thus more harmful than single lesions. Clustered lesions have only been investigated in dsDNA models. Introducing the term 'clustered damage to G-quadruplexes' we report here on the structural effects of multiple tetrahydrofuranyl abasic sites replacing loop adenines (A/AP) and tetrad guanines (G/AP) in quadruplexes formed by the human telomere d[AG(3)(TTAG(3))(3)] (htel-22) and d[TAG(3)(TTAG(3))(3)TT] (htel-25) in K+ solutions. Single to triple A/APs increased the population of parallel strands in their structures by stabilizing propeller type loops, shifting the antiparallel htel-22 into hybrid or parallel quadruplexes. In htel-25, the G/APs inhibited the formation of parallel strands and these adopted antiparallel topologies. Clustered G/AP and A/APs reduced the thermal stability of the wild-type htel-25. Depending on position, A/APs diminished or intensified the damaging effect of the G/APs. Taken together, clustered lesions can disrupt the topology and stability of the htel quadruplexes and restrict their conformational space. These in vitro results suggest that formation of clustered lesions in the chromosome capping structure can result in the unfolding of existing G-quadruplexes which can lead to telomere shortening.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

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Volume of the periodical

45

Issue of the periodical within the volume

8

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

4294-4305

UT code for WoS article

000400578600012

EID of the result in the Scopus database

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