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

0476265 - BFÚ 2018 RIV GB eng J - Článek v odborném periodiku
Kejnovská, Iva - Bednářová, Klára - Renčiuk, Daniel - Dvořáková, Zuzana - Školáková, Petra - Trantírek, L. - Fiala, R. - Vorlíčková, Michaela - Sagi, J.
Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes.
Nucleic Acids Research. Roč. 45, č. 8 (2017), s. 4294-4305. ISSN 0305-1048. E-ISSN 1362-4962
Grant CEP: GA MŠMT EF15_003/0000477; GA ČR GAP205/12/0466; GA ČR GA13-28310S; GA ČR(CZ) GA15-06785S; GA MŠMT(CZ) LQ1601
Institucionální podpora: RVO:68081707
Klíčová slova: dna-damage clusters * k+ solution * guanine quadruplexes
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 11.561, rok: 2017

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.
Trvalý link: http://hdl.handle.net/11104/0272809