Bending of DNA duplexes with mutation motifs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F19%3A00108081" target="_blank" >RIV/00216224:14740/19:00108081 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/65269705:_____/19:00071195

Výsledek na webu

<a href="https://watermark.silverchair.com/dsz013.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAn0wggJ5BgkqhkiG9w0BBwagggJqMIICZgIBADCCAl8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM2P_kZ8Bb6FuOfMVMAgEQgIICME8CSlfDtGUo2Ntsvr6SFHJpljqvpF_kdltgNIUNdU80L22" target="_blank" >https://watermark.silverchair.com/dsz013.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAn0wggJ5BgkqhkiG9w0BBwagggJqMIICZgIBADCCAl8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM2P_kZ8Bb6FuOfMVMAgEQgIICME8CSlfDtGUo2Ntsvr6SFHJpljqvpF_kdltgNIUNdU80L22</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/dnares/dsz013" target="_blank" >10.1093/dnares/dsz013</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Bending of DNA duplexes with mutation motifs

Popis výsledku v původním jazyce

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 &gt; 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.

Název v anglickém jazyce

Bending of DNA duplexes with mutation motifs

Popis výsledku anglicky

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 &gt; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

DNA RESEARCH

ISSN

1340-2838

e-ISSN

—

Svazek periodika

26

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

341-352

Kód UT WoS článku

000493011000005

EID výsledku v databázi Scopus

2-s2.0-85071704811