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.

Základní údaje

Originální název

Bending of DNA duplexes with mutation motifs

Autoři

RŮŽIČKA, Michal (203 Česká republika, domácí), Přemysl SOUČEK (203 Česká republika, domácí), Petr KULHÁNEK (203 Česká republika, domácí), Lenka RADOVÁ (203 Česká republika, domácí), L. FAJKUSOVA (203 Česká republika) a Kamila RÉBLOVÁ (203 Česká republika, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30101 Human genetics

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.009

Kód RIV

RIV/00216224:14740/19:00108081

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000493011000005

Klíčová slova anglicky

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

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 2. 2020 10:31, Mgr. Pavla Foltynová, Ph.D.

Anotace

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.

Návaznosti

GA16-11619S, projekt VaV

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

Investor: Grantová agentura ČR, Základní vlastnosti DNA mutačních coldspotů/hotspotů v genech asociovaných s dědičnými chorobami

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

RŮŽIČKA, Michal, Přemysl SOUČEK, Petr KULHÁNEK, Lenka RADOVÁ, L. FAJKUSOVA a Kamila RÉBLOVÁ. Bending of DNA duplexes with mutation motifs. DNA RESEARCH. OXFORD: OXFORD UNIV PRESS, 2019, roč. 26, č. 4, s. 341-352. ISSN 1340-2838. Dostupné z: 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 a Kamila RÉBLOVÁ. Bending of DNA duplexes with mutation motifs. \textit{DNA RESEARCH}. OXFORD: OXFORD UNIV PRESS, 2019, roč.~26, č.~4, s.~341-352. ISSN~1340-2838. Dostupné z: https://dx.doi.org/10.1093/dnares/dsz013.

Podrobný výpis o publikaci