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

Result code in 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>
Result on the web
<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>

Result language
angličtina
Original language name
Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate
Original language description
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.
Czech name
—
Czech description
—

Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/GA18-00258S" target="_blank" >GA18-00258S: The role of transposable elements in the dynamics of plant genomes</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Similar results(10)