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Article ; Online: NGS-determined molecular markers and disease burden metrics from ctDNA correlate with PFS in previously untreated DLBCL.

Tabari, Ehsan / Lovejoy, Alexander F / Lin, Hai / Bolen, Christopher R / Lor Saelee, Seng / Lefkowitz, Joshua P / Kurtz, David M / Bottos, Alessia / Nielsen, Tina G / Parreira, Joana M / Luong, Khai T

Leukemia & lymphoma

2024 Volume 65, Issue 5, Page(s) 618–628

Abstract: Personalized risk stratification and treatment may help improve outcomes among patients with diffuse large B-cell lymphoma (DLBCL). We developed a next-generation sequencing (NGS)-based method to assess a range of potential prognostic indicators, and ... ...

Abstract	Personalized risk stratification and treatment may help improve outcomes among patients with diffuse large B-cell lymphoma (DLBCL). We developed a next-generation sequencing (NGS)-based method to assess a range of potential prognostic indicators, and evaluated it using pretreatment plasma samples from 310 patients with previously untreated DLBCL from the GOYA trial (NCT01287741). Variant calls and DLBCL subtyping with the plasma-based method were concordant with corresponding tissue-based methods. Patients with a tumor burden greater than the median (
MeSH term(s)	Humans ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/blood ; Lymphoma, Large B-Cell, Diffuse/mortality ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; High-Throughput Nucleotide Sequencing ; Biomarkers, Tumor/blood ; Prognosis ; Male ; Female ; Middle Aged ; Aged ; Tumor Burden ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Mutation ; Aged, 80 and over
Chemical Substances	Circulating Tumor DNA ; Biomarkers, Tumor
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2024.2301924
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Article: Exploring the Roles of DNA Methylation in the Metal-Reducing Bacterium Shewanella oneidensis MR-1

Bendall, Matthew L / Luong, Khai / Wetmore, Kelly M / Blow, Matthew / Korlach, Jonas / Deutschbauer, Adam / Malmstrom, Rex R

Journal of bacteriology. 2013 Nov. 1, v. 195, no. 21

2013

Abstract: We performed whole-genome analyses of DNA methylation in Shewanella oneidensis MR-1 to examine its possible role in regulating gene expression and other cellular processes. Single-molecule real-time (SMRT) sequencing revealed extensive methylation of ... ...

Abstract	We performed whole-genome analyses of DNA methylation in Shewanella oneidensis MR-1 to examine its possible role in regulating gene expression and other cellular processes. Single-molecule real-time (SMRT) sequencing revealed extensive methylation of adenine (N6mA) throughout the genome. These methylated bases were located in five sequence motifs, including three novel targets for type I restriction/modification enzymes. The sequence motifs targeted by putative methyltranferases were determined via SMRT sequencing of gene knockout mutants. In addition, we found that S. oneidensis MR-1 cultures grown under various culture conditions displayed different DNA methylation patterns. However, the small number of differentially methylated sites could not be directly linked to the much larger number of differentially expressed genes under these conditions, suggesting that DNA methylation is not a major regulator of gene expression in S. oneidensis MR-1. The enrichment of methylated GATC motifs in the origin of replication indicates that DNA methylation may regulate genome replication in a manner similar to that seen in Escherichia coli. Furthermore, comparative analyses suggest that many Gammaproteobacteria, including all members of the Shewanellaceae family, may also utilize DNA methylation to regulate genome replication.
Keywords	DNA methylation ; Escherichia coli ; Shewanella oneidensis ; adenine ; bacteria ; bacteriology ; enzymes ; gene expression ; gene expression regulation ; gene targeting ; knockout mutants ; regulator genes ; replication origin
Language	English
Dates of publication	2013-1101
Size	p. 4966-4974.
Publishing place	American Society for Microbiology
Document type	Article
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00935-13
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Article ; Online: Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19.

Dannebaum, Richard / Suwalski, Phillip / Asgharian, Hosseinali / Du Zhipei, Gracie / Lin, Hai / Weiner, January / Holtgrewe, Manuel / Thibeault, Charlotte / Müller, Melina / Wang, Xiaomin / Karadeniz, Zehra / Saccomanno, Jacopo / Doehn, Jan-Moritz / Hübner, Ralf-Harto / Hinzmann, Bernd / Blüher, Anja / Siemann, Sandra / Telman, Dilduz / Suttorp, Norbert /

Witzenrath, Martin / Hippenstiel, Stefan / Skurk, Carsten / Poller, Wolfgang / Sander, Leif E / Beule, Dieter / Kurth, Florian / Guettouche, Toumy / Landmesser, Ulf / Berka, Jan / Luong, Khai / Rubelt, Florian / Heidecker, Bettina

EClinicalMedicine

2022 Volume 48, Page(s) 101438

Abstract: Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to ... ...

Abstract	Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response. Methods: In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19. Findings: Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden´s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple lymphocyte classes in disease progression. Interpretation: Adaptive immune receptor peripheral blood repertoire measures are associated with COVID-19 disease severity. Funding: The study was funded with grants from the Berlin Institute of Health (BIH).
Language	English
Publishing date	2022-05-14
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2022.101438
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Article ; Online: Identification of a

Doberenz, Sebastian / Eckweiler, Denitsa / Reichert, Olga / Jensen, Vanessa / Bunk, Boyke / Spröer, Cathrin / Kordes, Adrian / Frangipani, Emanuela / Luong, Khai / Korlach, Jonas / Heeb, Stephan / Overmann, Jörg / Kaever, Volkhard / Häussler, Susanne

mBio

2017 Volume 8, Issue 1

Abstract: DNA methylation is widespread among prokaryotes, and most DNA methylation reactions are catalyzed by adenine DNA methyltransferases, which are part of restriction-modification (R-M) systems. R-M systems are known for their role in the defense against ... ...

Abstract	DNA methylation is widespread among prokaryotes, and most DNA methylation reactions are catalyzed by adenine DNA methyltransferases, which are part of restriction-modification (R-M) systems. R-M systems are known for their role in the defense against foreign DNA; however, DNA methyltransferases also play functional roles in gene regulation. In this study, we used single-molecule real-time (SMRT) sequencing to uncover the genome-wide DNA methylation pattern in the opportunistic pathogen
MeSH term(s)	Adenine/analogs & derivatives ; Adenine/analysis ; Animals ; Chromatography, Liquid ; DNA Methylation ; Disease Models, Animal ; Epigenesis, Genetic ; Gene Expression Regulation, Bacterial ; Lepidoptera/microbiology ; Mass Spectrometry ; Promoter Regions, Genetic ; Pseudomonas Infections/microbiology ; Pseudomonas aeruginosa/enzymology ; Pseudomonas aeruginosa/growth & development ; Pseudomonas aeruginosa/metabolism ; Sequence Analysis, DNA ; Site-Specific DNA-Methyltransferase (Adenine-Specific)/metabolism ; Virulence
Chemical Substances	Site-Specific DNA-Methyltransferase (Adenine-Specific) (EC 2.1.1.72) ; Adenine (JAC85A2161) ; 6-methyladenine (W7IBY2BGAX)
Language	English
Publishing date	2017-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.02312-16
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Article ; Online: Comparative Genomics Reveals the Diversity of Restriction-Modification Systems and DNA Methylation Sites in Listeria monocytogenes.

Chen, Poyin / den Bakker, Henk C / Korlach, Jonas / Kong, Nguyet / Storey, Dylan B / Paxinos, Ellen E / Ashby, Meredith / Clark, Tyson / Luong, Khai / Wiedmann, Martin / Weimer, Bart C

Applied and environmental microbiology

2017 Volume 83, Issue 3

Abstract: Listeria monocytogenes is a bacterial pathogen that is found in a wide variety of anthropogenic and natural environments. Genome sequencing technologies are rapidly becoming a powerful tool in facilitating our understanding of how genotype, ... ...

Abstract	Listeria monocytogenes is a bacterial pathogen that is found in a wide variety of anthropogenic and natural environments. Genome sequencing technologies are rapidly becoming a powerful tool in facilitating our understanding of how genotype, classification phenotypes, and virulence phenotypes interact to predict the health risks of individual bacterial isolates. Currently, 57 closed L. monocytogenes genomes are publicly available, representing three of the four phylogenetic lineages, and they suggest that L. monocytogenes has high genomic synteny. This study contributes an additional 15 closed L. monocytogenes genomes that were used to determine the associations between the genome and methylome with host invasion magnitude. In contrast to previous findings, large chromosomal inversions and rearrangements were detected in five isolates at the chromosome terminus and within rRNA genes, including a previously undescribed inversion within rRNA-encoding regions. Each isolate's epigenome contained highly diverse methyltransferase recognition sites, even within the same serotype and methylation pattern. Eleven strains contained a single chromosomally encoded methyltransferase, one strain contained two methylation systems (one system on a plasmid), and three strains exhibited no methylation, despite the occurrence of methyltransferase genes. In three isolates a new, unknown DNA modification was observed in addition to diverse methylation patterns, accompanied by a novel methylation system. Neither chromosome rearrangement nor strain-specific patterns of epigenome modification observed within virulence genes were correlated with serotype designation, clonal complex, or in vitro infectivity. These data suggest that genome diversity is larger than previously considered in L. monocytogenes and that as more genomes are sequenced, additional structure and methylation novelty will be observed in this organism. Importance: Listeria monocytogenes is the causative agent of listeriosis, a disease which manifests as gastroenteritis, meningoencephalitis, and abortion. Among Salmonella, Escherichia coli, Campylobacter, and Listeria-causing the most prevalent foodborne illnesses-infection by L. monocytogenes carries the highest mortality rate. The ability of L. monocytogenes to regulate its response to various harsh environments enables its persistence and transmission. Small-scale comparisons of L. monocytogenes focusing solely on genome contents reveal a highly syntenic genome yet fail to address the observed diversity in phenotypic regulation. This study provides a large-scale comparison of 302 L. monocytogenes isolates, revealing the importance of the epigenome and restriction-modification systems as major determinants of L. monocytogenes phylogenetic grouping and subsequent phenotypic expression. Further examination of virulence genes of select outbreak strains reveals an unprecedented diversity in methylation statuses despite high degrees of genome conservation.
MeSH term(s)	DNA Methylation ; DNA Restriction-Modification Enzymes/genetics ; Genome, Bacterial ; Genomics ; Listeria monocytogenes/genetics ; Sequence Alignment ; Synteny
Chemical Substances	DNA Restriction-Modification Enzymes
Language	English
Publishing date	2017-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/AEM.02091-16
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Article ; Online: Detecting DNA modifications from SMRT sequencing data by modeling sequence context dependence of polymerase kinetic.

Feng, Zhixing / Fang, Gang / Korlach, Jonas / Clark, Tyson / Luong, Khai / Zhang, Xuegong / Wong, Wing / Schadt, Eric

PLoS computational biology

2013 Volume 9, Issue 3, Page(s) e1002935

Abstract: DNA modifications such as methylation and DNA damage can play critical regulatory roles in biological systems. Single molecule, real time (SMRT) sequencing technology generates DNA sequences as well as DNA polymerase kinetic information that can be used ... ...

Abstract	DNA modifications such as methylation and DNA damage can play critical regulatory roles in biological systems. Single molecule, real time (SMRT) sequencing technology generates DNA sequences as well as DNA polymerase kinetic information that can be used for the direct detection of DNA modifications. We demonstrate that local sequence context has a strong impact on DNA polymerase kinetics in the neighborhood of the incorporation site during the DNA synthesis reaction, allowing for the possibility of estimating the expected kinetic rate of the enzyme at the incorporation site using kinetic rate information collected from existing SMRT sequencing data (historical data) covering the same local sequence contexts of interest. We develop an Empirical Bayesian hierarchical model for incorporating historical data. Our results show that the model could greatly increase DNA modification detection accuracy, and reduce requirement of control data coverage. For some DNA modifications that have a strong signal, a control sample is not even needed by using historical data as alternative to control. Thus, sequencing costs can be greatly reduced by using the model. We implemented the model in a R package named seqPatch, which is available at https://github.com/zhixingfeng/seqPatch.
MeSH term(s)	Bayes Theorem ; Computational Biology/methods ; DNA Methylation ; DNA, Bacterial/chemistry ; DNA, Bacterial/genetics ; DNA, Bacterial/metabolism ; DNA-Directed DNA Polymerase/metabolism ; Escherichia coli/genetics ; Kinetics ; Models, Genetic ; Nucleic Acid Conformation ; Sequence Analysis, DNA/methods
Chemical Substances	DNA, Bacterial ; DNA-Directed DNA Polymerase (EC 2.7.7.7)
Language	English
Publishing date	2013-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1002935
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Article ; Online: Enhanced 5-methylcytosine detection in single-molecule, real-time sequencing via Tet1 oxidation.

Clark, Tyson A / Lu, Xingyu / Luong, Khai / Dai, Qing / Boitano, Matthew / Turner, Stephen W / He, Chuan / Korlach, Jonas

BMC biology

2013 Volume 11, Page(s) 4

Abstract: Background: DNA methylation serves as an important epigenetic mark in both eukaryotic and prokaryotic organisms. In eukaryotes, the most common epigenetic mark is 5-methylcytosine, whereas prokaryotes can have 6-methyladenine, 4-methylcytosine, or 5- ... ...

Abstract	Background: DNA methylation serves as an important epigenetic mark in both eukaryotic and prokaryotic organisms. In eukaryotes, the most common epigenetic mark is 5-methylcytosine, whereas prokaryotes can have 6-methyladenine, 4-methylcytosine, or 5-methylcytosine. Single-molecule, real-time sequencing is capable of directly detecting all three types of modified bases. However, the kinetic signature of 5-methylcytosine is subtle, which presents a challenge for detection. We investigated whether conversion of 5-methylcytosine to 5-carboxylcytosine using the enzyme Tet1 would enhance the kinetic signature, thereby improving detection. Results: We characterized the kinetic signatures of various cytosine modifications, demonstrating that 5-carboxylcytosine has a larger impact on the local polymerase rate than 5-methylcytosine. Using Tet1-mediated conversion, we show improved detection of 5-methylcytosine using in vitro methylated templates and apply the method to the characterization of 5-methylcytosine sites in the genomes of Escherichia coli MG1655 and Bacillus halodurans C-125. Conclusions: We have developed a method for the enhancement of directly detecting 5-methylcytosine during single-molecule, real-time sequencing. Using Tet1 to convert 5-methylcytosine to 5-carboxylcytosine improves the detection rate of this important epigenetic marker, thereby complementing the set of readily detectable microbial base modifications, and enhancing the ability to interrogate eukaryotic epigenetic markers.
MeSH term(s)	5-Methylcytosine/metabolism ; DNA Modification Methylases/metabolism ; DNA-Binding Proteins/metabolism ; Escherichia coli/enzymology ; Genome, Bacterial ; Kinetics ; Mixed Function Oxygenases ; Oxidation-Reduction ; Proto-Oncogene Proteins/metabolism ; Sequence Analysis, DNA ; Substrate Specificity
Chemical Substances	DNA-Binding Proteins ; Proto-Oncogene Proteins ; 5-Methylcytosine (6R795CQT4H) ; Mixed Function Oxygenases (EC 1.-) ; TET1 protein, human (EC 1.-) ; DNA Modification Methylases (EC 2.1.1.-)
Language	English
Publishing date	2013-01-22
Publishing country	England
Document type	Journal Article
ISSN	1741-7007
ISSN (online)	1741-7007
DOI	10.1186/1741-7007-11-4
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Article ; Online: Exploring the roles of DNA methylation in the metal-reducing bacterium Shewanella oneidensis MR-1.

Bendall, Matthew L / Luong, Khai / Wetmore, Kelly M / Blow, Matthew / Korlach, Jonas / Deutschbauer, Adam / Malmstrom, Rex R

Journal of bacteriology

2013 Volume 195, Issue 21, Page(s) 4966–4974

Abstract	We performed whole-genome analyses of DNA methylation in Shewanella oneidensis MR-1 to examine its possible role in regulating gene expression and other cellular processes. Single-molecule real-time (SMRT) sequencing revealed extensive methylation of adenine (N6mA) throughout the genome. These methylated bases were located in five sequence motifs, including three novel targets for type I restriction/modification enzymes. The sequence motifs targeted by putative methyltranferases were determined via SMRT sequencing of gene knockout mutants. In addition, we found that S. oneidensis MR-1 cultures grown under various culture conditions displayed different DNA methylation patterns. However, the small number of differentially methylated sites could not be directly linked to the much larger number of differentially expressed genes under these conditions, suggesting that DNA methylation is not a major regulator of gene expression in S. oneidensis MR-1. The enrichment of methylated GATC motifs in the origin of replication indicates that DNA methylation may regulate genome replication in a manner similar to that seen in Escherichia coli. Furthermore, comparative analyses suggest that many Gammaproteobacteria, including all members of the Shewanellaceae family, may also utilize DNA methylation to regulate genome replication.
MeSH term(s)	Chromosomes, Bacterial ; DNA Methylation/physiology ; DNA Mismatch Repair ; DNA, Bacterial/genetics ; DNA, Bacterial/metabolism ; Gene Expression Regulation, Bacterial ; Metals/chemistry ; Metals/metabolism ; Mutation ; Nucleic Acid Amplification Techniques ; Oxidation-Reduction ; Phylogeny ; Shewanella/classification ; Shewanella/genetics ; Shewanella/metabolism ; Transcriptome
Chemical Substances	DNA, Bacterial ; Metals
Language	English
Publishing date	2013-08-30
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00935-13
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Article ; Online: Live-cell imaging of single receptor composition using zero-mode waveguide nanostructures.

Richards, Christopher I / Luong, Khai / Srinivasan, Rahul / Turner, Stephen W / Dougherty, Dennis A / Korlach, Jonas / Lester, Henry A

Nano letters

2012 Volume 12, Issue 7, Page(s) 3690–3694

Abstract: We exploit the optical and spatial features of subwavelength nanostructures to examine individual receptors on the plasma membrane of living cells. Receptors were sequestered in portions of the membrane projected into zero-mode waveguides. Using single- ... ...

Abstract	We exploit the optical and spatial features of subwavelength nanostructures to examine individual receptors on the plasma membrane of living cells. Receptors were sequestered in portions of the membrane projected into zero-mode waveguides. Using single-step photobleaching of green fluorescent protein incorporated into individual subunits, the resulting spatial isolation was used to measure subunit stoichiometry in α4β4 and α4β2 nicotinic acetylcholine and P2X2 ATP receptors. We also show that nicotine and cytisine have differential effects on α4β2 stoichiometry.
MeSH term(s)	Alkaloids/chemistry ; Animals ; Azocines/chemistry ; Cell Line, Tumor ; Cell Membrane/chemistry ; Green Fluorescent Proteins/chemistry ; Mice ; Nanostructures/chemistry ; Nicotine/chemistry ; Particle Size ; Quinolizines/chemistry ; Receptors, Nicotinic/chemistry ; Receptors, Purinergic P2X2/chemistry ; Surface Properties
Chemical Substances	Alkaloids ; Azocines ; Quinolizines ; Receptors, Nicotinic ; Receptors, Purinergic P2X2 ; Green Fluorescent Proteins (147336-22-9) ; cytisine (53S5U404NU) ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2012-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1530-6992
ISSN (online)	1530-6992
DOI	10.1021/nl301480h
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Article ; Online: Defining the sequence requirements for the positioning of base J in DNA using SMRT sequencing.

Genest, Paul-Andre / Baugh, Loren / Taipale, Alex / Zhao, Wanqi / Jan, Sabrina / van Luenen, Henri G A M / Korlach, Jonas / Clark, Tyson / Luong, Khai / Boitano, Matthew / Turner, Steve / Myler, Peter J / Borst, Piet

Nucleic acids research

2015 Volume 43, Issue 4, Page(s) 2102–2115

Abstract: Base J (β-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. This highly restricted distribution must be co-determined by the ... ...

Abstract	Base J (β-D-glucosyl-hydroxymethyluracil) replaces 1% of T in the Leishmania genome and is only found in telomeric repeats (99%) and in regions where transcription starts and stops. This highly restricted distribution must be co-determined by the thymidine hydroxylases (JBP1 and JBP2) that catalyze the initial step in J synthesis. To determine the DNA sequences recognized by JBP1/2, we used SMRT sequencing of DNA segments inserted into plasmids grown in Leishmania tarentolae. We show that SMRT sequencing recognizes base J in DNA. Leishmania DNA segments that normally contain J also picked up J when present in the plasmid, whereas control sequences did not. Even a segment of only 10 telomeric (GGGTTA) repeats was modified in the plasmid. We show that J modification usually occurs at pairs of Ts on opposite DNA strands, separated by 12 nucleotides. Modifications occur near G-rich sequences capable of forming G-quadruplexes and JBP2 is needed, as it does not occur in JBP2-null cells. We propose a model whereby de novo J insertion is mediated by JBP2. JBP1 then binds to J and hydroxylates another T 13 bp downstream (but not upstream) on the complementary strand, allowing JBP1 to maintain existing J following DNA replication.
MeSH term(s)	DNA-Binding Proteins/metabolism ; Glucosides/analysis ; Glucosides/metabolism ; Leishmania/genetics ; Plasmids/genetics ; Protozoan Proteins/metabolism ; Sequence Analysis, DNA ; Uracil/analogs & derivatives ; Uracil/analysis ; Uracil/metabolism
Chemical Substances	DNA-Binding Proteins ; Glucosides ; J-specific DNA-binding protein, protozoa ; Protozoan Proteins ; 5-((glucopyranosyloxy)methyl)uracil (53910-96-6) ; Uracil (56HH86ZVCT)
Language	English
Publishing date	2015-02-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkv095
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