Bending of DNA duplexes with mutation motifs

J 2019

Bending of DNA duplexes with mutation motifs

RŮŽIČKA, Michal, Přemysl SOUČEK, Petr KULHÁNEK, Lenka RADOVÁ, L. FAJKUSOVA et. al.

Basic information

Original name

Bending of DNA duplexes with mutation motifs

Authors

RŮŽIČKA, Michal (203 Czech Republic, belonging to the institution), Přemysl SOUČEK (203 Czech Republic, belonging to the institution), Petr KULHÁNEK (203 Czech Republic, belonging to the institution), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), L. FAJKUSOVA (203 Czech Republic) and Kamila RÉBLOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

DNA RESEARCH, OXFORD, OXFORD UNIV PRESS, 2019, 1340-2838

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30101 Human genetics

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: 4.009

RIV identification code

RIV/00216224:14740/19:00108081

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1093/dnares/dsz013

UT WoS

000493011000005

Keywords in English

DNA bending; Muts protein; mutations; hotspots-coldspots; free energy calculations

Abstract

V originále

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.

Links

GA16-11619S, research and development project

Name: Základní vlastnosti DNA mutačních coldspotů/hotspotů v genech asociovaných s dědičnými chorobami

Investor: Czech Science Foundation

LM2015085, research and development project

Name: CERIT Scientific Cloud (Acronym: CERIT-SC)

Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

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

Citovat

RŮŽIČKA, Michal, Přemysl SOUČEK, Petr KULHÁNEK, Lenka RADOVÁ, L. FAJKUSOVA and Kamila RÉBLOVÁ. Bending of DNA duplexes with mutation motifs. 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.

@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.

Detailed Information on Publication Record