Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F18%3A00501657" target="_blank" >RIV/68081707:_____/18:00501657 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1101/gr.241257.118" target="_blank" >http://dx.doi.org/10.1101/gr.241257.118</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1101/gr.241257.118" target="_blank" >10.1101/gr.241257.118</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate

Popis výsledku v původním jazyce

DNA conformation may deviate from the classical B-form in similar to 13% of the human genome. Non-B DNA regulates many cellular processes, however, its effects on DNA polymerization speed and accuracy have not been investigated genome-wide. Such an inquiry is critical for understanding neurological diseases and cancer genome instability. Here, we present the first simultaneous examination of DNA polymerization kinetics and errors in the human genome sequenced with Single-Molecule Real-Time (SMRT) technology. We show that polymerization speed differs between non-B and B-DNA: It decelerates at G-quadruplexes and fluctuates periodically at disease-causing tandem repeats. Analyzing polymerization kinetics profiles, we predict and validate experimentally non-B DNA formation for a novel motif. We demonstrate that several non-B motifs affect sequencing errors (e.g., G-quadruplexes increase error rates), and that sequencing errors are positively associated with polymerase slowdown. Finally, we show that highly divergent G4 motifs have pronounced polymerization slowdown and high sequencing error rates, suggesting similar mechanisms for sequencing errors and germline mutations.

Název v anglickém jazyce

Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate

Popis výsledku anglicky

DNA conformation may deviate from the classical B-form in similar to 13% of the human genome. Non-B DNA regulates many cellular processes, however, its effects on DNA polymerization speed and accuracy have not been investigated genome-wide. Such an inquiry is critical for understanding neurological diseases and cancer genome instability. Here, we present the first simultaneous examination of DNA polymerization kinetics and errors in the human genome sequenced with Single-Molecule Real-Time (SMRT) technology. We show that polymerization speed differs between non-B and B-DNA: It decelerates at G-quadruplexes and fluctuates periodically at disease-causing tandem repeats. Analyzing polymerization kinetics profiles, we predict and validate experimentally non-B DNA formation for a novel motif. We demonstrate that several non-B motifs affect sequencing errors (e.g., G-quadruplexes increase error rates), and that sequencing errors are positively associated with polymerase slowdown. Finally, we show that highly divergent G4 motifs have pronounced polymerization slowdown and high sequencing error rates, suggesting similar mechanisms for sequencing errors and germline mutations.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA18-00258S" target="_blank" >GA18-00258S: Úloha transposonů v dynamice rostlinných genomů</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Genome Research

ISSN

1088-9051

e-ISSN

—

Svazek periodika

28

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1767-1778

Kód UT WoS článku

000451913800001

EID výsledku v databázi Scopus

—