Papers by Ronald Berezney
Supplementary Figure Legends 1-5, Table Legend 1 from Cytogenetic and cDNA Microarray Expression Analysis of MCF10 Human Breast Cancer Progression Cell Lines
Supplementary Figure Legends 1-5, Table Legend 1 from Cytogenetic and cDNA Microarray Expression ... more Supplementary Figure Legends 1-5, Table Legend 1 from Cytogenetic and cDNA Microarray Expression Analysis of MCF10 Human Breast Cancer Progression Cell Lines
Supplementary Table 2 from Cytogenetic and cDNA Microarray Expression Analysis of MCF10 Human Breast Cancer Progression Cell Lines
Supplementary Table 2 from Cytogenetic and cDNA Microarray Expression Analysis of MCF10 Human Bre... more Supplementary Table 2 from Cytogenetic and cDNA Microarray Expression Analysis of MCF10 Human Breast Cancer Progression Cell Lines
The Nuclear Matrix: A Structural Milieu for the Intranuclear Attachment and Replication of Eucaryotic DNA
Springer eBooks, 1981
Progress in recent years in defining a variety of specific proteins involved in the replication o... more Progress in recent years in defining a variety of specific proteins involved in the replication of procaryotic DNA has lead to the concept of the “replisome” in which a large number of proteins form a replication complex and move along the DNA strands at the replication forks (see Kornberg 1980 for an excellent discussion). Although our knowledge of eucaryotic replication is more limited, it is generally anticipated that replication in eucaryotic cells will prove to be at least as complex as procaryotic replication with regard to the number of factors involved and the integration of these factors during the replicative process.
Application of three dimensional image analysis to the mammalian cell nucleus
A three dimensional image segmentation and analysis system is proposed to study the confocal micr... more A three dimensional image segmentation and analysis system is proposed to study the confocal microscopy images of DNA replication sites in cell nuclei. The algorithm presented here includes detection of replication sites in 2D slices in the image and reconstructing 3D objects from 2D data. We also present a user interface to allow easy interaction with both the segmentation algorithm
Structural and functional organization of the nuclear matrix
Academic Press eBooks, 1995
This volume covers aspects of the structural organization and function at the nuclear matrix. Cha... more This volume covers aspects of the structural organization and function at the nuclear matrix. Chapters include discussions of the role of the nuclear matrix in transcription, nuclear matrix proteins and their functional role, and the architecture of the nuclear pore complex.
Cytochromes in bovine liver nuclear membranes
Biochemical and Biophysical Research Communications, Jun 1, 1971
Abstract Cytochrome a,a3 has been detected in highly purified nuclear membrane preparations. Nucl... more Abstract Cytochrome a,a3 has been detected in highly purified nuclear membrane preparations. Nuclear membranes resemble microsomal membranes in cytochrome b5 content but differ by the absence of the microsomal cytochrome P-450. Cytochrome a,a3 content in nuclear membranes is 30% that of mitochondria, and cytochrome b5 content is 33% of control microsomes.

Human Molecular Genetics, May 15, 2014
The interchromosomal spatial positionings of a subset of human chromosomes was examined in the hu... more The interchromosomal spatial positionings of a subset of human chromosomes was examined in the human breast cell line MCF10A (10A) and its malignant counterpart MCF10CA1a (CA1a). The nine chromosomes selected (#1, 4, 11, 12, 15, 16, 18, 21 and X) cover a wide range in size and gene density and compose ∼40% of the total human genome. Radial positioning of the chromosome territories (CT) was size dependent with certain of the CT more peripheral in CA1a. Each CT was in close proximity (interaction) with a similar number of other CT except the inactive CTXi. It had lower levels of interchromosomal partners in 10A which increased strikingly in CA1a. Major alterations from 10A to CA1a were detected in the pairwise interaction profiles which were subdivided into five types of altered interaction profiles: overall increase, overall decrease, switching from 1 to ≥2, vice versa or no change. A global data mining program termed the chromatic median calculated the most probable overall association network for the entire subset of CT. This interchromosomal network was drastically altered in CA1a with only 1 of 20 shared connections. We conclude that CT undergo multiple and preferred interactions with other CT in the cell nucleus and form preferred-albeit probabilistic-interchromosomal networks. This network of interactions is highly altered in malignant human breast cells. It is intriguing to consider the relationship of these alterations to the corresponding changes in the gene expression program of these malignant cancer cells.

Fidelity in Protein Synthesis
Journal of Biological Chemistry, Oct 1, 1968
Abstract The effect of ribosome species on ambiguity during the transfer of amino acids from Esch... more Abstract The effect of ribosome species on ambiguity during the transfer of amino acids from Escherichia coli aminoacyl transfer RNAs into protein has been examined under a variety of environmental conditions. Streptomycin greatly enhanced polyuridylic acid-directed transfer of leucine relative to phenylalanine (ambiguity ratio) with E. coli ribosomes, but had little effect with equivalent concentrations of reticulocyte ribosomes. The addition of E. coli supernatant fraction did not increase the ambiguity ratio obtained with reticulocyte ribosomes. In the presence of streptomycin, ambiguity was maximal at low concentrations of transfer RNA with E. coli ribosomes; transfer RNA concentration had a lesser effect on the low ambiguity obtained with reticulocyte ribosomes. Raising the magnesium concentration from 6 to 13 x 10-3 m increased the ambiguity ratio from 9 to 63% with E. coli ribosomes and from 0 to 25% with reticulocyte ribosomes. Ethanol increased the ambiguity ratio with E. coli ribosomes but not with reticulocyte ribosomes. The high fidelity of reticulocyte ribosomes was not restricted to leucine-phenylalanine ambiguity; although streptomycin caused a copolymer of uridylic and guanylic acid to miscode for arginine with E. coli ribosomes, this effect was not observed with reticulocyte ribosomes. These results show that streptomycin, a low concentration of transfer RNA, a high concentration of magnesium, and the addition of ethanol exert their miscoding effects at the ribosomal level. The fact that reticulocyte ribosomes are more resistant to these miscoding effects than E. coli ribosomes suggests that the ribosome plays an active role in codon recognition.
Biochemical and Biophysical Research Communications, 1987
Nuclear structure and function
Journal of Cellular Biochemistry, Aug 1, 1996
... American Society for Cell Biology VOLUME 53 Nuclear Structure and Function Edited by MiguelBe... more ... American Society for Cell Biology VOLUME 53 Nuclear Structure and Function Edited by MiguelBerrios University Microscopy Imaging Center and Department of Pharmacological Sciences School of Medicine, University Medical Center State University of New York Stony Brook ...
Biochimica Et Biophysica Acta - Bioenergetics, Dec 1, 1969
Journal of Biological Chemistry, Apr 1, 1987
Advances in enzyme regulation, 2002
Identification of a nuclear protein matrix
Biochemical and Biophysical Research Communications, Oct 1, 1974

DNA binding properties of the nuclear matrix and individual nuclear matrix proteins. Evidence for salt-resistant DNA binding sites
Journal of Biological Chemistry, Jun 1, 1991
The DNA binding characteristics of the rat nuclear matrix were investigated. A saturable and temp... more The DNA binding characteristics of the rat nuclear matrix were investigated. A saturable and temperature-dependent, salt-resistant DNA binding to the nuclear matrix was discovered, with 70-80% of total bound DNA resistant to extraction with high concentrations of salt at 37 degrees C, compared to less than 5% at 0 degrees C. The initial binding of DNA to nuclear matrix is sensitive to salt concentration, indicating a transition to a salt-resistant binding state. The nuclear matrix shows a preference for single-stranded DNA, both in saturation and competition assays, with little binding of RNA or double-stranded DNA. Further competition studies show a preference for matrix-attached DNA probably involving predominantly AT-rich sequences, while a specific sequence defined previously as a matrix-attached region (MAR; Cockerill, P. N., and Garrard, W. T. (1986) Cell 46, 273-282) only showed preference for a limited number of the total matrix binding sites. These results and estimates from saturation data of approximately 150,000 single-stranded DNA binding sites per matrix lead us to propose that the nuclear matrix contains different classes of DNA binding sites, each with a separate sequence specificity. Binding of DNA to individual matrix polypeptides separated on sodium dodecyl sulfate-polyacrylamide gels and transferred to nitrocellulose blots was also temperature-dependent, salt-resistant, and showed a preference for binding DNA over RNA and nuclear matrix DNA over total genomic DNA. Subnuclear fractionation experiments further demonstrated that the nuclear matrix is enriched in the subset of higher molecular weight (greater than 50,000) DNA binding proteins of isolated nuclei and correspondingly depleted of the lower molecular weight ones. Of the approximately 12 major proteins separated on nonequilibrium two-dimensional gels, 7 were identified as specific DNA binding proteins including lamins A and C (but not B), and the internal nuclear matrix proteins, matrins D, E, F, G, and 4.

Finding rigid sub-structure patterns from 3D point-sets
In this paper, we study the following rigid substructure pattern reconstruction problem: given a ... more In this paper, we study the following rigid substructure pattern reconstruction problem: given a set of n input structures (i.e. point-sets), partition each structure into k rigid sub-structures so that the nk rigid substructures can be grouped into k clusters with each of them containing exact one rigid substructure from every input structure and the total clustering cost is minimized, where the clustering cost of a cluster is the total distance between a pattern reconstructed for this cluster and every member rigid substructure. Different from most of the existing models for pattern reconstruction (where each input point-set is often treated as a single structure), our model views each input point-set as a collection of k rigid substructures, and aims to extract similar rigid substructures from each input point-set to form k rigid clusters. The problem is motivated by an interesting biological application for determining the topological structure of chromosomes inside the cell nucleus. We propose a highly effective and practical solution based on a number of new insights to pattern reconstruction, clustering, and motion detection. We validate our method on synthetic, biological and motion tracking datasets. Experimental results suggest that our approach yields a near optimal solution.

The Nuclear Matrix
Elsevier eBooks, 1997
Publisher Summary This chapter focuses on the basic properties of the nuclear matrix in relation ... more Publisher Summary This chapter focuses on the basic properties of the nuclear matrix in relation to the nuclear architecture, function, and regulation. The nuclear pore complexes are especially densely stained and channels of the nuclear matrix material appear to radiate from the nuclear interior to the nuclear pore complexes. The ultrastructural findings suggest a potentially close in situ association between actively replicating and transcribing chromatin and nuclear matrix components inside the functioning cell nucleus. It is suggested that a network of ribonucleoprotein particles and/or fibrils extends from the sites of transcription to final release through the nuclear pore complexes. These strands or channels of nuclear matrix structures may correspond to dynamic assembly lines for the coordinate transcription, splicing, processing, and transport of RNA. Results indicate that the overall organization of sites of replication, transcription, and posttranscriptional RNA transcripts and processing is strikingly maintained in cells extracted for the nuclear matrix. It is suggested that the in vitro nuclear matrix systems represent a valuable new approach for elucidating the relationships of genomic organization, function, and regulation in the mammalian cell nucleus.

Journal of Cellular Biochemistry, Mar 14, 2013
The replication timing of 9 genes commonly involved in cancer was investigated in the MCF10 cell ... more The replication timing of 9 genes commonly involved in cancer was investigated in the MCF10 cell lines for human breast cancer progression. Six of these nine genes are part of a constellation of tumor suppressor genes that play a major role in familial human breast cancer (TP53, ATM, PTEN, CHK2, BRCA1 and BRCA2). Three other genes are involved in a large number of human cancers including breast as either tumor suppressors (RB1 and RAD51) or as an oncogene (cMYC). Five of these nine genes (TP53, RAD51, ATM, PTEN and cMYC) show significant differences (p< 0.05) in replication timing between MCF10A normal human breast cells and the corresponding malignant MCF10CA1a cells. These differences are specific to the malignant state of the MCF10CA1a cells since there were no significant differences in the replication timing of these genes between normal MCF10A cells and the non-malignant cancer MCF10AT1 cells. Microarray analysis further demonstrated that three of these five genes (TP53, RAD51 and cMYC) showed significant changes in gene expression (≥ 2-fold) between normal and malignant cells. Our findings demonstrate an alteration in the replication timing of a small subset of cancer related genes in malignant breast cancer cells. These alterations partially correlate with the major transcriptional changes characteristic of the malignant state in these cells.

Biochemistry, Sep 8, 1987
Translocation of D N A during in vitro D N A synthesis on nuclear matrix bound replicational asse... more Translocation of D N A during in vitro D N A synthesis on nuclear matrix bound replicational assemblies from regenerating rat liver was determined by measuring the processivity (average number of nucleotides added following one productive binding event of the polymerase to the D N A template) of nuclear matrix bound D N A polymerase a with poly(dT).oligo(A) as template primer. The matrix-bound polymerase had an average processivity (28.4 nucleotides) that was severalfold higher than the bulk nuclear D N A polymerase a activity extracted during nuclear matrix preparation (8.9 nucleotides). ATP at 1 m M markedly enhanced the activity and processivity of the matrix-bound polymerase but not the corresponding salt-soluble enzyme. The majority of the ATP-dependent activity and processivity enhancement was completed by 100 FM A T P and included products ranging up to full template length (1000-1200 nucleotides). Average processivity of the net ATP-stimulated polymerase activity exceeded 80 nucleotides with virtually all the D N A products >50 nucleotides. Release of nuclear matrix bound D N A polymerase a! by sonication resulted in a loss of A T P stimulation of activity and a corresponding decrease in processivity to a level similar to that of the salt-soluble polymerase (6.8 nucleotides). All nucleoside di-and triphosphates were as effective as ATP. Stimulation of both activity and processivity by the nonhydrolyzable A T P analogues adenosine 5'-0-(3-thiotriphosphate), 5'-adenylyl imidodiphosphate, and adenosine 5'-0-( 1 -thiotriphosphate) further suggested that the hydrolysis of A T P is not required for enhancement to occur. A degree of specificity of nucleotide activation was indicated by the inability of nucleoside monophosphates, the A T P analogues

Nuclear matrix-bound DNA primase. Elucidation of an RNA priming system in nuclear matrix isolated from regenerating rat liver
Journal of Biological Chemistry, May 1, 1987
Recent findings in purified systems demonstrate the universality of DNA polymerase-primase comple... more Recent findings in purified systems demonstrate the universality of DNA polymerase-primase complexes which may function in the priming and continuation of eucaryotic DNA replication. In this report we characterize an in vitro, nuclear matrix-associated, priming and continuation system that can utilize either endogenous matrix-bound DNA or exogenous single-stranded DNA as template. 30-40% of total nuclear DNA primase activity was recovered in association with the isolated nuclear matrix fraction from regenerating rat liver. Matrix-bound primase catalyzed the alpha-amanitin, actinomycin D-resistant synthesis of oligonucleotide chains of 8-50 nucleotides on the endogenous template. At least a portion of the RNA primers were continued by DNA polymerase alpha with deoxynucleoside triphosphate incorporation up to 300-600 nucleotides. Nearest neighbor analysis revealed ribodeoxynucleotide covalent linkages in these RNA-DNA chains. The matrix-bound primase preferred single-stranded fd DNA as exogenous template over synthetic homopolymers and was strictly dependent on the presence of ribonucleoside triphosphates. Appropriate subfractionation revealed that the matrix-bound primase activity is exclusively localized in the nuclear matrix interior. The ability of primase and DNA polymerase to synthesize covalently linked RNA-DNA products demonstrates the potentially useful role of the nuclear matrix in vitro system for elucidating the organizational and functional properties of the eucaryotic replication apparatus in the cell nucleus.
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Papers by Ronald Berezney