Stephen D. Levene

Last updated
Stephen Daniel Levene
Born
New York, NY
Nationality American
Citizenship American
Alma mater Columbia University
Yale University
Known for Nucleic acid structure and function, physical genomics
Scientific career
Fields Chemistry, Biophysics, Bioengineering
Institutions University of Texas at Dallas
Lawrence Berkeley Laboratory
University of California, San Diego
Thesis Studies of Sequence-directed Bending and Flexibility in DNA (1985)
Doctoral advisor Donald M. Crothers
Website https://labs.utdallas.edu/levenelab/

Stephen Levene is an American biophysicist and professor of bioengineering, molecular biology, and physics at the University of Texas at Dallas. [1]

Contents

Early life and education

Levene was born in New York City and attended Horace Mann School and Andrew Hill High School in San Jose, California. He received his A.B. in Chemistry from Columbia University and his Ph.D. in Chemistry from Yale University. His doctoral work demonstrated and quantified the phenomenon of sequence-directed bending in DNA due to adenine-thymine tracts, [2] [3] and pioneered the use of Monte Carlo simulation to compute cyclization probabilities of DNA molecules having arbitrary preferred geometries. [4] [5] [6] Upon leaving Yale, Levene became an American Cancer Society postdoctoral fellow at UC San Diego with Bruno Zimm, where he worked on the physical mechanism of gel electrophoresis. [7] [8] [9]

Career

Research interests

Levene's research interests are broadly in the area of genome architecture and its maintenance by enzyme mechanisms and protein-DNA interactions. His work in this area began from the time he was a Staff Scientist at the Human Genome Center at Lawrence Berkeley National Laboratory, when he collaborated with Nicholas Cozzarelli's group on the structure and properties of supercoiled DNA [10] and DNA catenanes. [11] Levene's group has made both experimental and theoretical/computational contributions to understanding DNA topology and its relationship to local DNA structures, [12] [13] [14] DNA-loop formation, [15] [16] [17] site-specific DNA recombination, [18] [19] the structure of human telomeres, [20] [21] and extrachromosomal-circular DNA. [22]

Related Research Articles

<span class="mw-page-title-main">Agarose gel electrophoresis</span> Method for separation and analysis of biomolecules using agarose gel

Agarose gel electrophoresis is a method of gel electrophoresis used in biochemistry, molecular biology, genetics, and clinical chemistry to separate a mixed population of macromolecules such as DNA or proteins in a matrix of agarose, one of the two main components of agar. The proteins may be separated by charge and/or size, and the DNA and RNA fragments by length. Biomolecules are separated by applying an electric field to move the charged molecules through an agarose matrix, and the biomolecules are separated by size in the agarose gel matrix.

<span class="mw-page-title-main">DNA</span> Molecule that carries genetic information

Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

Molecular biology is a branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions.

DNA topoisomerases are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues in DNA arise due to the intertwined nature of its double-helical structure, which, for example, can lead to overwinding of the DNA duplex during DNA replication and transcription. If left unchanged, this torsion would eventually stop the DNA or RNA polymerases involved in these processes from continuing along the DNA helix. A second topological challenge results from the linking or tangling of DNA during replication. Left unresolved, links between replicated DNA will impede cell division. The DNA topoisomerases prevent and correct these types of topological problems. They do this by binding to DNA and cutting the sugar-phosphate backbone of either one or both of the DNA strands. This transient break allows the DNA to be untangled or unwound, and, at the end of these processes, the DNA backbone is resealed. Since the overall chemical composition and connectivity of the DNA do not change, the DNA substrate and product are chemical isomers, differing only in their topology.

<span class="mw-page-title-main">Gel electrophoresis of nucleic acids</span>

Nucleic acid electrophoresis is an analytical technique used to separate DNA or RNA fragments by size and reactivity. Nucleic acid molecules which are to be analyzed are set upon a viscous medium, the gel, where an electric field induces the nucleic acids to migrate toward the anode. The separation of these fragments is accomplished by exploiting the mobilities with which different sized molecules are able to pass through the gel. Longer molecules migrate more slowly because they experience more resistance within the gel. Because the size of the molecule affects its mobility, smaller fragments end up nearer to the anode than longer ones in a given period. After some time, the voltage is removed and the fragmentation gradient is analyzed. For larger separations between similar sized fragments, either the voltage or run time can be increased. Extended runs across a low voltage gel yield the most accurate resolution. Voltage is, however, not the sole factor in determining electrophoresis of nucleic acids.

<span class="mw-page-title-main">Nucleoid</span> Region within a prokaryotic cell containing genetic material

The nucleoid is an irregularly shaped region within the prokaryotic cell that contains all or most of the genetic material. The chromosome of a typical prokaryote is circular, and its length is very large compared to the cell dimensions, so it needs to be compacted in order to fit. In contrast to the nucleus of a eukaryotic cell, it is not surrounded by a nuclear membrane. Instead, the nucleoid forms by condensation and functional arrangement with the help of chromosomal architectural proteins and RNA molecules as well as DNA supercoiling. The length of a genome widely varies and a cell may contain multiple copies of it.

DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-polymerase or by helicase in front of the progressing replication fork. It is the only known enzyme to actively contribute negative supercoiling to DNA, while it also is capable of relaxing positive supercoils. It does so by looping the template to form a crossing, then cutting one of the double helices and passing the other through it before releasing the break, changing the linking number by two in each enzymatic step. This process occurs in bacteria, whose single circular DNA is cut by DNA gyrase and the two ends are then twisted around each other to form supercoils. Gyrase is also found in eukaryotic plastids: it has been found in the apicoplast of the malarial parasite Plasmodium falciparum and in chloroplasts of several plants. Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, novobiocin, albicidin, and ciprofloxacin.

<span class="mw-page-title-main">Obaid Siddiqi</span> Indian geneticist (1932–2013)

Obaid Siddiqi FRS was an Indian National Research Professor and the Founder-Director of the Tata Institute of Fundamental Research (TIFR) National Center for Biological Sciences. He made seminal contributions to the field of behavioural neurogenetics using the genetics and neurobiology of Drosophila.

<span class="mw-page-title-main">Homologous recombination</span> Genetic recombination between identical or highly similar strands of genetic material

Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids.

<i>Journal of Molecular Biology</i> Academic journal

The Journal of Molecular Biology is a biweekly peer-reviewed scientific journal covering all aspects of molecular biology. It was established in 1959 and is published by Elsevier. The editor-in-chief is Peter Wright.

<span class="mw-page-title-main">Cohesin</span> Protein complex that regulates the separation of sister chromatids during cell division

Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3. Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.

Charles R. Cantor is an American molecular geneticist who, in conjunction with David Schwartz, developed pulse field gel electrophoresis for very large DNA molecules. Cantor's three-volume book Biophysical Chemistry, co-authored with Paul Schimmel, was an influential textbook in the 1980s and 1990s.

The L-arabinose operon, also called the ara or araBAD operon, is an operon required for the breakdown of the five-carbon sugar L-arabinose in Escherichia coli. The L-arabinose operon contains three structural genes: araB, araA, araD, which encode for three metabolic enzymes that are required for the metabolism of L-arabinose. AraB (ribulokinase), AraA, and AraD produced by these genes catalyse conversion of L-arabinose to an intermediate of the pentose phosphate pathway, D-xylulose-5-phosphate.

In molecular biology, a displacement loop or D-loop is a DNA structure where the two strands of a double-stranded DNA molecule are separated for a stretch and held apart by a third strand of DNA. An R-loop is similar to a D-loop, but in this case the third strand is RNA rather than DNA. The third strand has a base sequence which is complementary to one of the main strands and pairs with it, thus displacing the other complementary main strand in the region. Within that region the structure is thus a form of triple-stranded DNA. A diagram in the paper introducing the term illustrated the D-loop with a shape resembling a capital "D", where the displaced strand formed the loop of the "D".

<span class="mw-page-title-main">Donald Crothers</span>

Donald Crothers was a professor of chemistry at Yale University in the United States. He was best known for his work on nucleic acid structure and function.

<span class="mw-page-title-main">R-loop</span> Three-stranded nucleic acid structure

An R-loop is a three-stranded nucleic acid structure, composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA. R-loops may be formed in a variety of circumstances and may be tolerated or cleared by cellular components. The term "R-loop" was given to reflect the similarity of these structures to D-loops; the "R" in this case represents the involvement of an RNA moiety.

Saccharolobus solfataricus is a species of thermophilic archaeon. It was transferred from the genus Sulfolobus to the new genus Saccharolobus with the description of Saccharolobus caldissimus in 2018.

<span class="mw-page-title-main">Topologically associating domain</span> Self-interacting genomic region

A topologically associating domain (TAD) is a self-interacting genomic region, meaning that DNA sequences within a TAD physically interact with each other more frequently than with sequences outside the TAD. The median size of a TAD in mouse cells is 880 kb, and they have similar sizes in non-mammalian species. Boundaries at both side of these domains are conserved between different mammalian cell types and even across species and are highly enriched with CCCTC-binding factor (CTCF) and cohesin. In addition, some types of genes appear near TAD boundaries more often than would be expected by chance.

<span class="mw-page-title-main">Cruciform DNA</span>

Cruciform DNA is a form of non-B DNA, or an alternative DNA structure. The formation of cruciform DNA requires the presence of palindromes called inverted repeat sequences. These inverted repeats contain a sequence of DNA in one strand that is repeated in the opposite direction on the other strand. As a result, inverted repeats are self-complementary and can give rise to structures such as hairpins and cruciforms. Cruciform DNA structures require at least a six nucleotide sequence of inverted repeats to form a structure consisting of a stem, branch point and loop in the shape of a cruciform, stabilized by negative DNA supercoiling.

Elizabeth Lynn Zechiedrich is a professor in the department of Molecular Virology and Microbiology at Baylor College of Medicine. Her laboratory's research considers the structure-function properties of DNA and DNA topoisomerases. She was elected to the National Academy of Inventors in 2017.

References

  1. ↑ UT-Dallas Bioengineering Web Page
  2. ↑ Marini, Joan C.; Levene, Stephen D.; Crothers, Donald M.; Englund, Paul T. (1982). "Bent helical structure in kinetoplast DNA". Proceedings of the National Academy of Sciences. 79 (24): 7664–7668. Bibcode:1982PNAS...79.7664M. doi: 10.1073/pnas.79.24.7664 . PMC   347408 . PMID   16593261.
  3. ↑ Levene, Stephen D.; Ming Wu, Hen; Crothers, Donald M. (1986). "Bending and flexibility of kinetoplast DNA". Biochemistry. 25 (14): 3988–3995. doi:10.1021/bi00362a003. PMID   3017412.
  4. ↑ Levene, Stephen D.; Crothers, Donald M. (1986). "Ring closure probabilities for DNA fragments by Monte Carlo simulation". Journal of Molecular Biology. 189 (1): 61–72. doi:10.1016/0022-2836(86)90381-5. PMID   3783680.
  5. ↑ Levene, Stephen D.; Crothers, Donald M. (1986). "Topological distributions and the torsional rigidity of DNA". Journal of Molecular Biology. 189 (1): 73–83. doi:10.1016/0022-2836(86)90382-7. PMID   3783681.
  6. ↑ Crothers, Donald M.; Drak, Jacqueline; Kahn, Jason D.; Levene, Stephen D. (1992). "[1] DNA bending, flexibility, and helical repeat by cyclization kinetics". DNA Structures Part B: Chemical and Electrophoretic Analysis of DNA. Methods in Enzymology. Vol. 212. pp. 3–29. doi:10.1016/0076-6879(92)12003-9. ISBN   9780121821135. PMID   1518450.
  7. ↑ Levene, SD; Zimm, BH (1987). "Separations of open-circular DNA using pulsed-field electrophoresis". Proceedings of the National Academy of Sciences. 84 (12): 4054–7. Bibcode:1987PNAS...84.4054L. doi: 10.1073/pnas.84.12.4054 . PMC   305020 . PMID   3295875.
  8. ↑ Levene, Stephen D.; Zimm, Bruno H. (1989). "Understanding the Anomalous Electrophoresis of Bent DNA Molecules: A Reptation Model". Science. 245 (4916): 396–399. Bibcode:1989Sci...245..396L. doi:10.1126/science.2756426. PMID   2756426.
  9. ↑ Zimm, BH; Levene, SD (1992). "Problems and prospects in the theory of gel electrophoresis of DNA". Quarterly Reviews of Biophysics. 25 (2): 171–204. doi:10.1017/s0033583500004662. PMID   1518924. S2CID   27976751.
  10. ↑ Vologodskii, AV; Levene, SD; Klenin, KV; Frank-Kamenetskii, M; Cozzarelli, NR (1992). "Conformational and thermodynamic properties of supercoiled DNA". Journal of Molecular Biology. 227 (4): 1224–43. doi:10.1016/0022-2836(92)90533-p. PMID   1433295.
  11. ↑ Levene, SD; Donahue, C; Boles, TC; Cozzarelli, NR (1995). "Analysis of the structure of dimeric DNA catenanes by electron microscopy". Biophysical Journal. 69 (3): 1036–45. Bibcode:1995BpJ....69.1036L. doi:10.1016/S0006-3495(95)79978-7. PMC   1236332 . PMID   8519958.
  12. ↑ Tsen, H; Levene, SD (1997). "Supercoiling-dependent flexibility of adenosine-tract-containing DNA detected by a topological method". Proceedings of the National Academy of Sciences. 94 (7): 2817–22. Bibcode:1997PNAS...94.2817T. doi: 10.1073/pnas.94.7.2817 . PMC   20279 . PMID   9096303.
  13. ↑ Tsen, H; Levene, SD (2004). "Analysis of chemical and enzymatic cleavage frequencies in supercoiled DNA". Journal of Molecular Biology. 336 (5): 1087–102. doi:10.1016/j.jmb.2003.12.079. PMID   15037071.
  14. ↑ Giovan, Stefan M.; Scharein, Robert G.; Hanke, Andreas; Levene, Stephen D. (2014). "Free-energy calculations for semi-flexible macromolecules: Applications to DNA knotting and looping". The Journal of Chemical Physics. 141 (17): 174902. Bibcode:2014JChPh.141q4902G. doi:10.1063/1.4900657. PMC   4241824 . PMID   25381542.
  15. ↑ Zhang, Yongli; McEwen, Abbye E.; Crothers, Donald M.; Levene, Stephen D. (2006). "Statistical-Mechanical Theory of DNA Looping". Biophysical Journal. 90 (6): 1903–1912. Bibcode:2006BpJ....90.1903Z. doi:10.1529/biophysj.105.070490. PMC   1386771 . PMID   16361335.
  16. ↑ Zhang, Yongli; McEwen, Abbye E.; Crothers, Donald M.; Levene, Stephen D. (2006). "Analysis of In-Vivo LacR-Mediated Gene Repression Based on the Mechanics of DNA Looping". PLOS ONE. 1 (1): e136. Bibcode:2006PLoSO...1..136Z. doi: 10.1371/journal.pone.0000136 . PMC   1762422 . PMID   17205140.
  17. ↑ Giovan, Stefan M.; Hanke, Andreas; Levene, Stephen D. (2015). "DNA cyclization and looping in the wormlike limit: Normal modes and the validity of the harmonic approximation". Biopolymers. 103 (9): 528–538. doi:10.1002/bip.22683. PMC   6815668 . PMID   26014845.
  18. ↑ Huffman, Kenneth E.; Levene, Stephen D. (1999). "DNA-sequence asymmetry directs the alignment of recombination sites in the FLP synaptic complex". Journal of Molecular Biology. 286 (1): 1–13. doi:10.1006/jmbi.1998.2468. PMID   9931245.
  19. ↑ Vetcher, Alexandre A.; Lushnikov, Alexander Y.; Navarra-Madsen, Junalyn; Scharein, Robert G.; Lyubchenko, Yuri L.; Darcy, Isabel K.; Levene, Stephen D. (2006). "DNA Topology and Geometry in FLP and Cre Recombination". Journal of Molecular Biology. 357 (4): 1089–1104. doi:10.1016/j.jmb.2006.01.037. PMID   16483600.
  20. ↑ Wright, WE; Tesmer, VM; Huffman, KE; Levene, SD; Shay, JW (November 1997). "Normal human chromosomes have long G-rich telomeric overhangs at one end". Genes & Development. 11 (21): 2801–9. doi:10.1101/gad.11.21.2801. PMC   316649 . PMID   9353250.
  21. ↑ Huffman, KE; Levene, SD; Tesmer, VM; Shay, JW; Wright, WE (2000). "Telomere shortening is proportional to the size of the G-rich telomeric 3'-overhang". The Journal of Biological Chemistry. 275 (26): 19719–22. doi: 10.1074/jbc.M002843200 . PMID   10787419.
  22. ↑ Shoura, Massa J.; Gabdank, Idan; Hansen, Loren; Merker, Jason; Gotlib, Jason; Levene, Stephen D.; Fire, Andrew Z. (2017). "Intricate and Cell Type-Specific Populations of Endogenous Circular DNA (EccDNA) in Caenorhabditis elegans and Homo sapiens". G3: Genes, Genomes, Genetics. 7 (10): 3295–3303. doi:10.1534/g3.117.300141. PMC   5633380 . PMID   28801508.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.