Journal ArticleGenome Res · January 5, 2026
Epigenetic mechanisms contribute to gene regulation by altering chromatin accessibility through changes in transcription factor (TF) and nucleosome occupancy across the genome. Despite numerous studies focusing on changes in gene expression, the intricate ...
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Journal ArticleCell · October 2, 2025
Despite the remarkable fidelity of eukaryotic DNA replication, nucleotide misincorporation errors occur in every replication cycle, generating mutations that drive genetic diseases and genome evolution. Here, we show that transcription factor (TF) proteins ...
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Journal ArticleJ Biol Chem · May 2025
Spt6-Spn1 is an essential histone chaperone complex that associates with RNA Polymerase II (RNAPII) and reassembles nucleosomes during gene transcription. While the interaction between Spt6 and Spn1 is important for its histone deposition and transcription ...
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Journal ArticleGenome Res · December 27, 2023
Proper maintenance of epigenetic information after replication is dependent on the rapid assembly and maturation of chromatin. Chromatin Assembly Complex 1 (CAF-1) is a conserved histone chaperone that deposits (H3-H4)2 tetramers as part of the replication ...
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Journal ArticleGenes (Basel) · December 16, 2021
Origins of DNA replication are specified by the ordered recruitment of replication factors in a cell-cycle-dependent manner. The assembly of the pre-replicative complex in G1 and the pre-initiation complex prior to activation in S phase are well characteri ...
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Journal ArticleGenes Dev · October 1, 2021
Prior to initiation of DNA replication, the eukaryotic helicase, Mcm2-7, must be activated to unwind DNA at replication start sites in early S phase. To study helicase activation within origin chromatin, we constructed a conditional mutant of the polymeras ...
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Journal ArticleNucleic Acids Res · August 20, 2021
Chromatin is a tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the binding locations and occupancy levels of d ...
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Journal ArticleMol Cell · July 15, 2021
Wang et al. (2021) comprehensively map DNA replication initiation events across the human genome using single-molecule optical resolution mapping and find that initiation events are randomly distributed across broad initiation zones that are only utilized ...
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Journal ArticleGenome Res · June 2021
Though the sequence of the genome within each eukaryotic cell is essentially fixed, it exists within a complex and changing chromatin state. This state is determined, in part, by the dynamic binding of proteins to the DNA. These proteins-including histones ...
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Journal ArticleGenome Res · May 2021
We interrogated at nucleotide resolution the spatiotemporal order of chromatin changes that occur immediately following a site-specific double-strand break (DSB) upstream of the PHO5 locus and its subsequent repair by nonhomologous end joining (NHEJ). We o ...
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ConferenceRes Comput Mol Biol · May 2020
Chromatin is the tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the binding locations and level of occupancy ...
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Journal ArticleNat Commun · April 14, 2020
The environmental carcinogen urethane exhibits a profound specificity for pulmonary tumors driven by an oncogenic Q61L/R mutation in the gene Kras. Similarly, the frequency, isoform, position, and substitution of oncogenic RAS mutations are often unique to ...
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Journal ArticleGenome Res · July 2019
Proper regulation and maintenance of the epigenome is necessary to preserve genome function. However, in every cell division, the epigenetic state is disassembled and then reassembled in the wake of the DNA replication fork. Chromatin restoration on nascen ...
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Journal ArticlePLoS Genet · May 2019
Repetitive DNA sequences within eukaryotic heterochromatin are poorly transcribed and replicate late in S-phase. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ...
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Journal ArticleGenome Biol · March 11, 2019
Following publication of the original article [1], the authors reported the following errors. ...
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Journal ArticleGenome Res · November 2018
Chromatin structure has emerged as a key contributor to spatial and temporal control over the initiation of DNA replication. However, despite genome-wide correlations between early replication of gene-rich, accessible euchromatin and late replication of ge ...
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Journal ArticleElife · March 21, 2017
Eukaryotic replication origin licensing, activation and timing are influenced by chromatin but a mechanistic understanding is lacking. Using reconstituted nucleosomal DNA replication assays, we assessed the impact of nucleosomes on replication initiation. ...
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Journal ArticleNucleic Acids Res · March 17, 2017
DNA replication requires the recruitment of a pre-replication complex facilitated by Origin Recognition Complex (ORC) onto the chromatin during G1 phase of the cell cycle. The ORC-associated protein (ORCA/LRWD1) stabilizes ORC on chromatin. Here, we evalua ...
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Journal ArticleNucleic Acids Res · September 6, 2016
The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication. Monomethylation of H4K20 (H4K20me1) is mediated by the cell cycle-regulated histone methyltransferase PR-Set7. ...
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Journal ArticleGenes Dev · August 1, 2016
For more than three decades, investigators have sought to identify the precise locations where DNA replication initiates in mammalian genomes. The development of molecular and biochemical approaches to identify start sites of DNA replication (origins) base ...
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Journal ArticleMol Cell Biol · July 1, 2016
FACT (facilitates chromatin transcription) consists of two essential subunits, Spt16 and Pob3, and functions as a histone chaperone. Mutation of spt16 results in a global loss of nucleosomes as well as aberrant transcription. Here, we show that the majorit ...
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Chapter · January 1, 2016
DNA replication is an essential cell cycle-regulated process necessary for the accurate duplication of the genome. DNA replication begins at cis-acting replicator loci (replication origins) that are distributed throughout each of the eukaryotic chromosomes ...
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Journal ArticleMol Cell Biol · June 2015
The DNA replication checkpoint (DRC) monitors and responds to stalled replication forks to prevent genomic instability. How core replication factors integrate into this phosphorylation cascade is incompletely understood. Here, through analysis of a unique ...
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Journal ArticleCell · April 9, 2015
The fundamental unit of DNA replication, the replicon, is governed by a cis-acting replicator sequence and a trans-activating initiator factor. Despite the increased size and complexity of eukaryotic genomes, eukaryotic DNA replication continues to be guid ...
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Journal ArticleEMBO J · February 12, 2015
Eukaryotic replication origins are defined by the ORC-dependent loading of the Mcm2-7 helicase complex onto chromatin in G1. Paradoxically, there is a vast excess of Mcm2-7 relative to ORC assembled onto chromatin in G1. These excess Mcm2-7 complexes exhib ...
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Journal ArticleGenes Dev · January 15, 2015
Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly underst ...
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Journal ArticleJ Clin Invest · January 2015
The KRAS gene is commonly mutated in human cancers, rendering the encoded small GTPase constitutively active and oncogenic. This gene has the unusual feature of being enriched for rare codons, which limit protein expression. Here, to determine the effect o ...
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Journal ArticleGenome Res · November 2014
Mutational heterogeneity must be taken into account when reconstructing evolutionary histories, calibrating molecular clocks, and predicting links between genes and disease. Selective pressures and various DNA transactions have been invoked to explain the ...
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Journal ArticleNature · August 28, 2014
Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our unde ...
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Journal ArticleGenome Biol · August 28, 2014
BACKGROUND: Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at the organismal level, but are common in immortalized cell lines and tumors, where they may be an advantage to cells. In orde ...
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Journal ArticleGenome Res · July 2014
DNA replication is a dynamic process that occurs in a temporal order along each of the chromosomes. A consequence of the temporally coordinated activation of replication origins is the establishment of broad domains (>100 kb) that replicate either early or ...
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Journal ArticleCold Spring Harb Perspect Biol · August 1, 2013
The size of a eukaryotic genome presents a unique challenge to the cell: package and organize the DNA to fit within the confines of the nucleus while at the same time ensuring sufficient dynamics to allow access to specific sequences and features such as g ...
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Journal ArticleCurr Biol · January 7, 2013
Oncogenic mutations in the small Ras GTPases KRas, HRas, and NRas render the proteins constitutively GTP bound and active, a state that promotes cancer. Ras proteins share ~85% amino acid identity, are activated by and signal through the same proteins, and ...
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Journal ArticleDev Dyn · November 2012
BACKGROUND: Microarray studies have shown that the E2F transcription factor influences the expression of many genes but it is unclear how many of these targets are important for E2F-mediated control of cell proliferation. RESULTS: We assembled a collection ...
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Journal ArticleMethods · June 2012
Chromatin Immunoprecipitation (ChIP) is a powerful tool for the identification and characterization of protein-DNA interactions in vivo. ChIP has been utilized to study diverse nuclear processes such as transcription regulation, chromatin modification, DNA ...
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Journal ArticleGenome Res · January 2012
Precise DNA replication is crucial for genome maintenance, yet this process has been inherently difficult to study on a genome-wide level in untransformed differentiated metazoan cells. To determine how metazoan DNA replication can be repressed, we examine ...
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Journal ArticleProc Natl Acad Sci U S A · November 8, 2011
We have combined standard micrococcal nuclease (MNase) digestion of nuclei with a modified protocol for constructing paired-end DNA sequencing libraries to map both nucleosomes and subnucleosome-sized particles at single base-pair resolution throughout the ...
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Journal ArticleGenes Dev · July 1, 2011
In metazoans, how replication origins are specified and subsequently activated is not well understood. Drosophila amplicons in follicle cells (DAFCs) are genomic regions that undergo rereplication to increase DNA copy number. We identified all DAFCs by com ...
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Journal ArticleCrit Rev Biochem Mol Biol · April 2011
DNA replication is an essential cell cycle event required for the accurate and timely duplication of the chromosomes. It is essential that the genome is replicated accurately and completely within the confines of S-phase. Failure to completely copy the gen ...
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Journal ArticleNature · March 24, 2011
Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melan ...
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Journal ArticleNature · March 24, 2011
Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide has successfully identified specific subtypes of regulatory elemen ...
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Journal ArticleGenome Res · February 2011
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DNA replication initiates from thousands of start sites throughout the Drosophila genome and must be coordinated with other ongoing nuclear processes such as transcription to ensure genetic and epigenetic inheritance. Considerable progress has been made to ...
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Journal ArticleGenome Res · February 2011
Polyploid or polytene cells, which have more than 2C DNA content, are widespread throughout nature and present in most differentiated Drosophila tissues. These cells also can display differential replication, that is, genomic regions of increased or decrea ...
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Journal ArticleScience · December 24, 2010
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To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal p ...
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Journal ArticlePLoS Genet · September 9, 2010
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To ensure genomic integrity, the genome must be duplicated exactly once per cell cycle. Disruption of replication licensing mechanisms may lead to re-replication and genomic instability. Cdt1, also known as Double-parked (Dup) in Drosophila, is a key regul ...
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Journal ArticleGenes Dev · July 1, 2010
The origin recognition complex (ORC) binds to the specific positions on chromosomes that serve as DNA replication origins. Although ORC is conserved from yeast to humans, the DNA sequence elements that specify ORC binding are not. In particular, metazoan O ...
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Journal ArticleGenes Dev · April 15, 2010
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The origin recognition complex (ORC) specifies replication origin location. The Saccharomyces cerevisiae ORC recognizes the ARS (autonomously replicating sequence) consensus sequence (ACS), but only a subset of potential genomic sites are bound, suggesting ...
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Journal ArticlePLoS Biol · February 23, 2010
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Extensive departures from balanced gene dose in aneuploids are highly deleterious. However, we know very little about the relationship between gene copy number and expression in aneuploid cells. We determined copy number and transcript abundance (expressio ...
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Journal ArticleGenome Res · February 2010
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The origin recognition complex (ORC) is an essential DNA replication initiation factor conserved in all eukaryotes. In Saccharomyces cerevisiae, ORC binds to specific DNA elements; however, in higher eukaryotes, ORC exhibits little sequence specificity in ...
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Journal ArticlePLoS Genet · January 15, 2010
In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this bias in the bacterium Bacillus su ...
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Journal ArticleNature · June 18, 2009
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UNLABELLED: Despite the successes of genomics, little is known about how genetic information produces complex organisms. A look at the crucial functional elements of fly and worm genomes could change that. SUPPLEMENTARY INFORMATION: The online version of t ...
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Journal ArticleEMBO J · December 12, 2007
Post-translational modifications of histones are involved in transcript initiation and elongation. Methylation of lysine 36 of histone H3 (H3K36me) resides promoter distal at transcribed regions in Saccharomyces cerevisiae and is thought to prevent spuriou ...
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Journal ArticleGenes Dev · November 15, 2007
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Myb-MuvB (MMB)/dREAM is a nine-subunit complex first described in Drosophila as a repressor of transcription, dependent on E2F2 and the RBFs. Myb, an integral member of MMB, curiously plays no role in the silencing of the test genes previously analyzed. Mo ...
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Journal ArticleProc Natl Acad Sci U S A · October 23, 2007
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Gene clusters amplified in the ovarian follicle cells of Drosophila serve as powerful models for metazoan DNA replication. In response to developmental signals, specific genomic regions undergo amplification by repeated firing of replication origins and bi ...
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Journal ArticleMol Biol Cell · May 2006
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DNA replication must be tightly controlled during each cell cycle to prevent unscheduled replication and ensure proper genome maintenance. The currently known controls that prevent re-replication act redundantly to inhibit pre-replicative complex (pre-RC) ...
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Journal ArticleProc Natl Acad Sci U S A · May 3, 2005
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Chromosomes in human cancer cells are expected to initiate replication from predictably localized origins, firing reproducibly at discrete times in S phase. Replication products obtained from HeLa cells at different stages of S phase were hybridized to cDN ...
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Journal ArticleChromosome Res · 2005
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Recent advances in DNA microarray technology have enabled eukaryotic replication to be studied at whole-chromosome and genome-wide levels. These studies have provided new insights into the mechanisms that influence origin selection and the temporally co-or ...
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Journal ArticleGenes Dev · December 15, 2004
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The mechanisms by which metazoan origins of DNA replication are defined, regulated, and influenced by chromosomal events remain poorly understood. To gain insights into these mechanisms, we developed a systematic approach using a Drosophila high-resolution ...
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Journal ArticleGenes Dev · June 1, 2004
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The covalent modification of nucleosomal histones has emerged as a major determinant of chromatin structure and gene activity. To understand the interplay between various histone modifications, including acetylation and methylation, we performed a genome-w ...
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Journal ArticleJ Cell Biol · October 28, 2002
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Chorion gene amplification in the ovaries of Drosophila melanogaster is a powerful system for the study of metazoan DNA replication in vivo. Using a combination of high-resolution confocal and deconvolution microscopy and quantitative realtime PCR, we foun ...
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Journal ArticleEMBO J · April 2, 2001
Wild-type yeast mitochondrial DNA (mtDNA) is inherited biparentally, whereas mtDNA of hypersuppressive petite mutants is inherited uniparentally in crosses to strains with wild-type mtDNA. Genomes of hypersuppressive petites contain a conserved ori sequenc ...
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Journal ArticleEMBO J · February 15, 2000
Mitochondrial DNA (mtDNA) is inherited as a protein-DNA complex (the nucleoid). We show that activation of the general amino acid response pathway in rho(+) and rho(-) petite cells results in an increased number of nucleoids without an increase in mtDNA co ...
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Journal ArticleProc Natl Acad Sci U S A · June 9, 1998
Abf2p is a high mobility group (HMG) protein found in yeast mitochondria that is required for the maintenance of wild-type (rho+) mtDNA in cells grown on fermentable carbon sources, and for efficient recombination of mtDNA markers in crosses. Here, we show ...
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Journal ArticleMol Cell Biol · October 1997
The palindromic Tetrahymena ribosomal DNA (rDNA) minichromosome is amplified 10,000-fold during development. Subsequent vegetative replication is cell cycle regulated. rDNA replication differs fundamentally in cycling vegetative and nondividing amplifying ...
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Journal ArticleMol Cell Biol · August 1997
Two-dimensional gel electrophoresis was used to study replication of the Tetrahymena thermophila ribosomal DNA (rDNA) minichromosome. During vegetative growth, the rDNA is replicated exclusively from origins in the 5' nontranscribed spacer (NTS). Whereas r ...
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Journal ArticlePlant Physiol · December 1994
Fructose-1,6-biphosphate aldolase (ALD) and enolase (ENO) from the glycolytic pathway and pyruvate decarboxylase (PDC) and alcohol dehydrogenase 2 (ADH2) from the ethanolic fermentative pathway, are enzymes previously identified as among those synthesized ...
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