-
Something wrong with this record ?
Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate
WM. Guiblet, MA. Cremona, M. Cechova, RS. Harris, I. Kejnovská, E. Kejnovsky, K. Eckert, F. Chiaromonte, KD. Makova,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1991 to 6 months ago
Freely Accessible Science Journals
from 1991-08-01 to 1 year ago
PubMed Central
from 1997 to 6 months ago
Europe PubMed Central
from 1997 to 6 months ago
Open Access Digital Library
from 1991-08-01
Open Access Digital Library
from 1991-08-01
PubMed
30401733
DOI
10.1101/gr.241257.118
Knihovny.cz E-resources
- MeSH
- DNA chemistry MeSH
- G-Quadruplexes MeSH
- Genomics * methods standards MeSH
- Kinetics MeSH
- Nucleic Acid Conformation * MeSH
- Humans MeSH
- Mutation MeSH
- Nucleotide Motifs MeSH
- DNA Replication MeSH
- Reproducibility of Results MeSH
- Sequence Analysis, DNA * methods MeSH
- High-Throughput Nucleotide Sequencing * methods standards MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
DNA conformation may deviate from the classical B-form in ∼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.
Department of Biology Penn State University University Park Pennsylvania 16802 USA
Department of Pathology Penn State University College of Medicine Hershey Pennsylvania 17033 USA
Department of Statistics Penn State University University Park Pennsylvania 16802 USA
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc19028109
- 003
- CZ-PrNML
- 005
- 20190819113533.0
- 007
- ta
- 008
- 190813s2018 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1101/gr.241257.118 $2 doi
- 035 __
- $a (PubMed)30401733
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Guiblet, Wilfried M $u Bioinformatics and Genomics Graduate Program, Penn State University, University Park, Pennsylvania 16802, USA.
- 245 10
- $a Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate / $c WM. Guiblet, MA. Cremona, M. Cechova, RS. Harris, I. Kejnovská, E. Kejnovsky, K. Eckert, F. Chiaromonte, KD. Makova,
- 520 9_
- $a DNA conformation may deviate from the classical B-form in ∼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.
- 650 _2
- $a DNA $x chemie $7 D004247
- 650 _2
- $a replikace DNA $7 D004261
- 650 _2
- $a G-kvadruplexy $7 D054856
- 650 12
- $a genomika $x metody $x normy $7 D023281
- 650 12
- $a vysoce účinné nukleotidové sekvenování $x metody $x normy $7 D059014
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a kinetika $7 D007700
- 650 _2
- $a mutace $7 D009154
- 650 12
- $a konformace nukleové kyseliny $7 D009690
- 650 _2
- $a nukleotidové motivy $7 D059372
- 650 _2
- $a reprodukovatelnost výsledků $7 D015203
- 650 12
- $a sekvenční analýza DNA $x metody $7 D017422
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Cremona, Marzia A $u Department of Statistics, Penn State University, University Park, Pennsylvania 16802, USA.
- 700 1_
- $a Cechova, Monika $u Department of Biology, Penn State University, University Park, Pennsylvania 16802, USA.
- 700 1_
- $a Harris, Robert S $u Department of Biology, Penn State University, University Park, Pennsylvania 16802, USA.
- 700 1_
- $a Kejnovská, Iva $u Department of Biophysics of Nucleic Acids, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.
- 700 1_
- $a Kejnovsky, Eduard $u Department of Plant Developmental Genetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.
- 700 1_
- $a Eckert, Kristin $u Department of Pathology, Penn State University, College of Medicine, Hershey, Pennsylvania 17033, USA.
- 700 1_
- $a Chiaromonte, Francesca $u Department of Statistics, Penn State University, University Park, Pennsylvania 16802, USA. Sant'Anna School of Advanced Studies, 56127 Pisa, Italy.
- 700 1_
- $a Makova, Kateryna D $u Department of Biology, Penn State University, University Park, Pennsylvania 16802, USA.
- 773 0_
- $w MED00001911 $t Genome research $x 1549-5469 $g Roč. 28, č. 12 (2018), s. 1767-1778
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/30401733 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20190813 $b ABA008
- 991 __
- $a 20190819113807 $b ABA008
- 999 __
- $a ok $b bmc $g 1433258 $s 1066569
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2018 $b 28 $c 12 $d 1767-1778 $e 20181106 $i 1549-5469 $m Genome research $n Genome Res $x MED00001911
- LZP __
- $a Pubmed-20190813
