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@article{1607141,
author = {Růžička, Michal and Souček, Přemysl and Kulhánek, Petr and Radová, Lenka and Fajkusova, L. and Réblová, Kamila},
article_location = {OXFORD},
article_number = {4},
doi = {http://dx.doi.org/10.1093/dnares/dsz013},
keywords = {DNA bending; Muts protein; mutations; hotspots-coldspots; free energy calculations},
language = {eng},
issn = {1340-2838},
journal = {DNA RESEARCH},
title = {Bending of DNA duplexes with mutation motifs},
url = {https://watermark.silverchair.com/dsz013.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAn0wggJ5BgkqhkiG9w0BBwagggJqMIICZgIBADCCAl8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM2P_kZ8Bb6FuOfMVMAgEQgIICME8CSlfDtGUo2Ntsvr6SFHJpljqvpF_kdltgNIUNdU80L22},
volume = {26},
year = {2019}
}
TY - JOUR
ID - 1607141
AU - Růžička, Michal - Souček, Přemysl - Kulhánek, Petr - Radová, Lenka - Fajkusova, L. - Réblová, Kamila
PY - 2019
TI - Bending of DNA duplexes with mutation motifs
JF - DNA RESEARCH
VL - 26
IS - 4
SP - 341-352
EP - 341-352
PB - OXFORD UNIV PRESS
SN - 13402838
KW - DNA bending
KW - Muts protein
KW - mutations
KW - hotspots-coldspots
KW - free energy calculations
UR - https://watermark.silverchair.com/dsz013.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAn0wggJ5BgkqhkiG9w0BBwagggJqMIICZgIBADCCAl8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM2P_kZ8Bb6FuOfMVMAgEQgIICME8CSlfDtGUo2Ntsvr6SFHJpljqvpF_kdltgNIUNdU80L22
L2 - https://watermark.silverchair.com/dsz013.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAn0wggJ5BgkqhkiG9w0BBwagggJqMIICZgIBADCCAl8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM2P_kZ8Bb6FuOfMVMAgEQgIICME8CSlfDtGUo2Ntsvr6SFHJpljqvpF_kdltgNIUNdU80L22
N2 - Mutations can be induced by environmental factors but also arise spontaneously during DNA replication or due to deamination of methylated cytosines at CpG dinucleotides. Sites where mutations occur with higher frequency than would be expected by chance are termed hotspots while sites that contain mutations rarely are termed coldspots. Mutations are permanently scanned and repaired by repair systems. Among them, the mismatch repair targets base pair mismatches, which are discriminated from canonical base pairs by probing altered elasticity of DNA. Using biased molecular dynamics simulations, we investigated the elasticity of coldspots and hotspots motifs detected in human genes associated with inherited disorders, and also of motifs with Czech population hotspots and de novo mutations. Main attention was paid to mutations leading to G/T and A+/C pairs. We observed that hotspots without CpG/CpHpG sequences are less flexible than coldspots, which indicates that flexible sequences are more effectively repaired. In contrary, hotspots with CpG/CpHpG sequences exhibited increased flexibility as coldspots. Their mutability is more likely related to spontaneous deamination of methylated cytosines leading to C > T mutations, which are primarily targeted by base excision repair. We corroborated conclusions based on computer simulations by measuring melting curves of hotspots and coldspots containing G/T mismatch.
ER -
RŮŽIČKA, Michal, Přemysl SOUČEK, Petr KULHÁNEK, Lenka RADOVÁ, L. FAJKUSOVA and Kamila RÉBLOVÁ. Bending of DNA duplexes with mutation motifs. \textit{DNA RESEARCH}. OXFORD: OXFORD UNIV PRESS, 2019, vol.~26, No~4, p.~341-352. ISSN~1340-2838. Available from: https://dx.doi.org/10.1093/dnares/dsz013.
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