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

J 2017

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

KEJNOVSKÁ, Iva, Klára BEDNÁŘOVÁ, Daniel RENČIUK, Zuzana DVOŘÁKOVÁ, Petra ŠKOLÁKOVÁ et. al.

Basic information

Original name

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

Authors

KEJNOVSKÁ, Iva (203 Czech Republic), Klára BEDNÁŘOVÁ (203 Czech Republic), Daniel RENČIUK (203 Czech Republic), Zuzana DVOŘÁKOVÁ (203 Czech Republic), Petra ŠKOLÁKOVÁ (203 Czech Republic), Lukáš TRANTÍREK (203 Czech Republic, guarantor, belonging to the institution), Radovan FIALA (203 Czech Republic, belonging to the institution), Michaela VORLÍČKOVÁ (203 Czech Republic) and J. SAGI (840 United States of America)

Edition

Nucleic Acids Research, Oxford, Oxford University Press, 2017, 0305-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.561

RIV identification code

RIV/00216224:14740/17:00095078

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1093/nar/gkx191

UT WoS

000400578600012

Keywords in English

DNA-DAMAGE CLUSTERS; K+ SOLUTION; GUANINE QUADRUPLEXES; IONIZING-RADIATION; BASE LESIONS; CELLS; 8-OXOGUANINE; SEQUENCE; TETRAD; SITES

Abstract

V originále

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.

Links

GA13-28310S, research and development project

Name: Evolučně konzervované strukturní vlastnosti centromerické a telomerické DNA

Investor: Czech Science Foundation

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

KEJNOVSKÁ, Iva, Klára BEDNÁŘOVÁ, Daniel RENČIUK, Zuzana DVOŘÁKOVÁ, Petra ŠKOLÁKOVÁ, Lukáš TRANTÍREK, Radovan FIALA, Michaela VORLÍČKOVÁ and J. SAGI. Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes. Nucleic Acids Research. Oxford: Oxford University Press, 2017, vol. 45, No 8, p. 4294-4305. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkx191.

@article{1392894,
   author = {Kejnovská, Iva and Bednářová, Klára and Renčiuk, Daniel and Dvořáková, Zuzana and Školáková, Petra and Trantírek, Lukáš and Fiala, Radovan and Vorlíčková, Michaela and Sagi, J.},
   article_location = {Oxford},
   article_number = {8},
   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},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes},
   url = {https://watermark.silverchair.com/gkx191.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAbEwggGtBgkqhkiG9w0BBwagggGeMIIBmgIBADCCAZMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMPhjm4qncd9c3wayHAgEQgIIBZHNy50Rs-TH7Fcsl3VTJ-F4kBqgbb6qbJ4tdfAMDkpZjURB},
   volume = {45},
   year = {2017}
}

TY  - JOUR
ID  - 1392894
AU  - Kejnovská, Iva - Bednářová, Klára - Renčiuk, Daniel - Dvořáková, Zuzana - Školáková, Petra - Trantírek, Lukáš - Fiala, Radovan - Vorlíčková, Michaela - Sagi, J.
PY  - 2017
TI  - Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes
JF  - Nucleic Acids Research
VL  - 45
IS  - 8
SP  - 4294-4305
EP  - 4294-4305
PB  - Oxford University Press
SN  - 03051048
KW  - DNA-DAMAGE CLUSTERS
KW  - K+ SOLUTION
KW  - GUANINE QUADRUPLEXES
KW  - IONIZING-RADIATION
KW  - BASE LESIONS
KW  - CELLS
KW  - 8-OXOGUANINE
KW  - SEQUENCE
KW  - TETRAD
KW  - SITES
UR  - https://watermark.silverchair.com/gkx191.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAbEwggGtBgkqhkiG9w0BBwagggGeMIIBmgIBADCCAZMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMPhjm4qncd9c3wayHAgEQgIIBZHNy50Rs-TH7Fcsl3VTJ-F4kBqgbb6qbJ4tdfAMDkpZjURB
L2  - https://watermark.silverchair.com/gkx191.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAbEwggGtBgkqhkiG9w0BBwagggGeMIIBmgIBADCCAZMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMPhjm4qncd9c3wayHAgEQgIIBZHNy50Rs-TH7Fcsl3VTJ-F4kBqgbb6qbJ4tdfAMDkpZjURB
N2  - 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.
ER  -

KEJNOVSKÁ, Iva, Klára BEDNÁŘOVÁ, Daniel RENČIUK, Zuzana DVOŘÁKOVÁ, Petra ŠKOLÁKOVÁ, Lukáš TRANTÍREK, Radovan FIALA, Michaela VORLÍČKOVÁ and J. SAGI. Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2017, vol.~45, No~8, p.~4294-4305. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkx191.

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