Publication details

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

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Authors

KEJNOVSKÁ Iva BEDNÁŘOVÁ Klára RENČIUK Daniel DVOŘÁKOVÁ Zuzana ŠKOLÁKOVÁ Petra TRANTÍREK Lukáš FIALA Radovan VORLÍČKOVÁ Michaela SAGI J.

Year of publication 2017
Type Article in Periodical
Magazine / Source Nucleic Acids Research
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://watermark.silverchair.com/gkx191.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAbEwggGtBgkqhkiG9w0BBwagggGeMIIBmgIBADCCAZMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMPhjm4qncd9c3wayHAgEQgIIBZHNy50Rs-TH7Fcsl3VTJ-F4kBqgbb6qbJ4tdfAMDkpZjURB
Doi http://dx.doi.org/10.1093/nar/gkx191
Keywords DNA-DAMAGE CLUSTERS; K+ SOLUTION; GUANINE QUADRUPLEXES; IONIZING-RADIATION; BASE LESIONS; CELLS; 8-OXOGUANINE; SEQUENCE; TETRAD; SITES
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.
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