Roger D. Kornberg

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Roger Kornberg

ForMemRS [1]
Roger Kornberg (Nobel Medicine or Physiology 2006) in Stockholm, June 2016.jpg
Kornberg in 2016
Born (1947-04-24) April 24, 1947 (age 76)
St. Louis, Missouri, US
Alma mater
Known forTransmission of genetic information from DNA to RNA
SpouseYahli Lorch
Children3[ citation needed ]
Awards
Scientific career
Fields Structural biology
Institutions
Thesis The Diffusion of Phospholipids in Membranes  (1972)
Doctoral advisor Harden M. McConnell [3]
Website kornberg.stanford.edu
Signature
RogerDKornberg.jpg

Roger David Kornberg (born April 24, [4] 1947) is an American biochemist and professor of structural biology at Stanford University School of Medicine. Kornberg was awarded the Nobel Prize in Chemistry in 2006 for his studies of the process by which genetic information from DNA is copied to RNA, "the molecular basis of eukaryotic transcription." [5] [6] [7] [8] [9] [10]

Contents

Education and early life

Kornberg was born in St. Louis, Missouri, into a Jewish family, [11] the eldest son of biochemist Arthur Kornberg, who won the Nobel Prize, and Sylvy Kornberg who was also a biochemist. He earned his bachelor's degree in chemistry from Harvard University in 1967 and his Ph.D. in chemical physics from Stanford in 1972 supervised by Harden M. McConnell. [3]

Career

Kornberg became a postdoctoral research fellow at the Laboratory of Molecular Biology in Cambridge, England and then an Assistant Professor of Biological Chemistry at Harvard Medical School in 1976, before moving to his present position as Professor of Structural Biology at Stanford Medical School in 1978. [12] Since 2004, Kornberg has been the editor of the Annual Review of Biochemistry . [13]

Research

Kornberg in 2006 Roger.Kornberg.JPG
Kornberg in 2006
Roger D. Kornberg (third from left) with Andrew Fire, George Smoot, Dick Cheney, Craig Mello and John C. Mather Vice President Dick Cheney meets with the 2006 U.S. Nobel Laureates, Thursday, November 30, 2006.jpg
Roger D. Kornberg (third from left) with Andrew Fire, George Smoot, Dick Cheney, Craig Mello and John C. Mather

Kornberg identified the role of RNA polymerase II and other proteins in DNA transcription, creating three-dimensional images of the protein cluster using X-ray crystallography. [14]

Kornberg and his research group have made several fundamental discoveries concerning the mechanisms and regulation of eukaryotic transcription. While a graduate student working with Harden McConnell at Stanford in the late 1960s, he discovered the "flip-flop" and lateral diffusion of phospholipids in bilayer membranes. Meanwhile, as a postdoctoral fellow working with Aaron Klug and Francis Crick at the MRC in the 1970s, Kornberg discovered the nucleosome as the basic protein complex packaging chromosomal DNA in the nucleus of eukaryotic cells (chromosomal DNA is often termed "chromatin" when it is bound to proteins in this manner). [15] Within the nucleosome, Kornberg found that roughly 200 bp of DNA are wrapped around an octamer of histone proteins. With Yahli Lorch, Kornberg showed that a nucleosome on a promoter prevents the initiation of transcription, leading to the recognition of a functional role for the nucleosome, which serves as a general gene repressor. [16]

Kornberg's research group at Stanford later succeeded in the development of a faithful transcription system from baker's yeast, a simple unicellular eukaryote, which they then used to isolate in a purified form all of the several dozen proteins required for the transcription process. Through the work of Kornberg and others, it has become clear that these protein components are remarkably conserved across the full spectrum of eukaryotes, from yeast to human cells. [17]

Using this system, Kornberg made the major discovery that transmission of gene regulatory signals to the RNA polymerase machinery is accomplished by an additional protein complex that they dubbed Mediator. [18] As noted by the Nobel Prize committee, "the great complexity of eukaryotic organisms is actually enabled by the fine interplay between tissue-specific substances, enhancers in the DNA and Mediator. The discovery of Mediator is therefore a true milestone in the understanding of the transcription process." [19]

At the same time as Kornberg was pursuing these biochemical studies of the transcription process, he devoted two decades to the development of methods to visualize the atomic structure of RNA polymerase and its associated protein components. [14] Initially, Kornberg took advantage of expertise with lipid membranes gained from his graduate studies to devise a technique for the formation of two-dimensional protein crystals on lipid bilayers. These 2D crystals could then be analyzed using electron microscopy to derive low-resolution images of the protein's structure. Eventually, Kornberg was able to use X-ray crystallography to solve the 3-dimensional structure of RNA polymerase at atomic resolution. [20] [21] He has recently extended these studies to obtain structural images of RNA polymerase associated with accessory proteins. [22] Through these studies, Kornberg has created an actual picture of how transcription works at a molecular level. According to the Nobel Prize committee, "the truly revolutionary aspect of the picture Kornberg has created is that it captures the process of transcription in full flow. What we see is an RNA-strand being constructed, and hence the exact positions of the DNA, polymerase and RNA during this process." [23]

Lipids membrane

As a graduate student at Stanford University, Kornberg's studied the rotation of phospholipids and defined for the first time the dynamics of lipids in the membrane. [24] Kornberg called the movement of lipid from one leaflet to the other flip-flop because he had studied only a few years before electronic circuit elements called flip-flops. The term gave rise to the naming of proteins called flippases and floppases. [25]

Industrial collaborations

Kornberg has served on the Scientific Advisory Boards of the following companies: Cocrystal Discovery, Inc (Chairman), ChromaDex Corporation (Chairman), StemRad, Ltd, Oplon Ltd (Chairman), and Pacific Biosciences. Kornberg has also been a director for the following companies: OphthaliX Inc., Protalix BioTherapeutics, Can-Fite BioPharma, Ltd, Simploud and Teva Pharmaceutical Industries, Ltd.

Awards and honors

Kornberg has received the following awards:


See also

Related Research Articles

Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.

<span class="mw-page-title-main">RNA</span> Family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and DNA deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

<span class="mw-page-title-main">Transcription (biology)</span> Process of copying a segment of DNA into RNA

Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA, while at least 80% of mammalian genomic DNA can be actively transcribed, with the majority of this 80% considered to be ncRNA.

<span class="mw-page-title-main">RNA polymerase</span> Enzyme that synthesizes RNA from DNA

In molecular biology, RNA polymerase, or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template.

<span class="mw-page-title-main">DNA polymerase</span> Form of DNA replication

A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create two identical DNA duplexes from a single original DNA duplex. During this process, DNA polymerase "reads" the existing DNA strands to create two new strands that match the existing ones. These enzymes catalyze the chemical reaction

<span class="mw-page-title-main">Transcription preinitiation complex</span> Complex of proteins necessary for gene transcription in eukaryotes and archaea

The preinitiation complex is a complex of approximately 100 proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. The preinitiation complex positions RNA polymerase II at gene transcription start sites, denatures the DNA, and positions the DNA in the RNA polymerase II active site for transcription.

<span class="mw-page-title-main">Robert G. Roeder</span>

Robert G. Roeder is an American biochemist. He is known as a pioneer scientist in eukaryotic transcription. He discovered three distinct nuclear RNA polymerases in 1969 and characterized many proteins involved in the regulation of transcription, including basic transcription factors and the first mammalian gene-specific activator over five decades of research. He is the recipient of the Gairdner Foundation International Award in 2000, the Albert Lasker Award for Basic Medical Research in 2003, and the Kyoto Prize in 2021. He currently serves as Arnold and Mabel Beckman Professor and Head of the Laboratory of Biochemical and Molecular Biology at The Rockefeller University.

<span class="mw-page-title-main">RNA polymerase II</span> Protein complex that transcribes DNA

RNA polymerase II is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryotic cells. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. A wide range of transcription factors are required for it to bind to upstream gene promoters and begin transcription.

<span class="mw-page-title-main">General transcription factor</span> Class of protein transcription factors

General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites (promoter) on DNA to activate transcription of genetic information from DNA to messenger RNA. GTFs, RNA polymerase, and the mediator constitute the basic transcriptional apparatus that first bind to the promoter, then start transcription. GTFs are also intimately involved in the process of gene regulation, and most are required for life.

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Aled Morgan Edwards is the founder and Chief Executive of the Structural Genomics Consortium, a charitable public-private partnership. He is Professor of Medical Genetics and Medical Biophysics at the University of Toronto, Visiting Professor of Chemical Biology at the University of Oxford, and Adjunct Professor at McGill University.

<span class="mw-page-title-main">Eukaryotic transcription</span> Transcription is heterocatalytic function of DNA

Eukaryotic transcription is the elaborate process that eukaryotic cells use to copy genetic information stored in DNA into units of transportable complementary RNA replica. Gene transcription occurs in both eukaryotic and prokaryotic cells. Unlike prokaryotic RNA polymerase that initiates the transcription of all different types of RNA, RNA polymerase in eukaryotes comes in three variations, each translating a different type of gene. A eukaryotic cell has a nucleus that separates the processes of transcription and translation. Eukaryotic transcription occurs within the nucleus where DNA is packaged into nucleosomes and higher order chromatin structures. The complexity of the eukaryotic genome necessitates a great variety and complexity of gene expression control.

<span class="mw-page-title-main">Mediator (coactivator)</span>

Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. It was discovered in 1990 in the lab of Roger D. Kornberg, recipient of the 2006 Nobel Prize in Chemistry. Mediator complexes interact with transcription factors and RNA polymerase II. The main function of mediator complexes is to transmit signals from the transcription factors to the polymerase.

Dame Jean Olwen Thomas, is a Welsh biochemist, former Master of St Catharine's College, Cambridge, and Chancellor of Swansea University.

<span class="mw-page-title-main">Transcription factor II B</span> Mammalian protein found in Homo sapiens

Transcription factor II B (TFIIB) is a general transcription factor that is involved in the formation of the RNA polymerase II preinitiation complex (PIC) and aids in stimulating transcription initiation. TFIIB is localised to the nucleus and provides a platform for PIC formation by binding and stabilising the DNA-TBP complex and by recruiting RNA polymerase II and other transcription factors. It is encoded by the TFIIB gene, and is homologous to archaeal transcription factor B and analogous to bacterial sigma factors.

FACT is a heterodimeric protein complex that affects eukaryotic RNA polymerase II transcription elongation both in vitro and in vivo. It was discovered in 1998 as a factor purified from human cells that was essential for productive, in vitro Pol II transcription on a chromatinized DNA template.

<span class="mw-page-title-main">Macromolecular assembly</span>

The term macromolecular assembly (MA) refers to massive chemical structures such as viruses and non-biologic nanoparticles, cellular organelles and membranes and ribosomes, etc. that are complex mixtures of polypeptide, polynucleotide, polysaccharide or other polymeric macromolecules. They are generally of more than one of these types, and the mixtures are defined spatially, and with regard to their underlying chemical composition and structure. Macromolecules are found in living and nonliving things, and are composed of many hundreds or thousands of atoms held together by covalent bonds; they are often characterized by repeating units. Assemblies of these can likewise be biologic or non-biologic, though the MA term is more commonly applied in biology, and the term supramolecular assembly is more often applied in non-biologic contexts. MAs of macromolecules are held in their defined forms by non-covalent intermolecular interactions, and can be in either non-repeating structures, or in repeating linear, circular, spiral, or other patterns. The process by which MAs are formed has been termed molecular self-assembly, a term especially applied in non-biologic contexts. A wide variety of physical/biophysical, chemical/biochemical, and computational methods exist for the study of MA; given the scale of MAs, efforts to elaborate their composition and structure and discern mechanisms underlying their functions are at the forefront of modern structure science.

<span class="mw-page-title-main">I. Robert Lehman</span> American biochemist (born 1924)

Israel Robert Lehman is a Lithuanian-born American biochemist. His work primarily focused on the study of DNA replication and repair, as well as the replication of phages and the herpes virus. Notably, he collaborated with Arthur Konrberg in the discovery of DNA polymerase and the reaction responsible for genetic material replication. He also made major contributions in characterizing the process of homologous recombination. He served as the head of the Department of Biochemistry at Stanford University from 1974 to 1979 and again from 1984 to 1986. Lehman was awarded the Merk Prize by the American Society for Biochemistry and Molecular Biology.

Sylvy Kornberg née Sylvia Ruth Levy (1917–1986) was an American biochemist who carried out research on DNA replication and polyphosphate synthesis. She discovered and characterized polyphosphate kinase (PPK), an enzyme that helps build long chains of phosphate groups called polyphosphate (PolyP) that play a variety of metabolic and regulatory functions. She worked closely with her husband and research partner, Arthur Kornberg, contributing greatly to the characterization of DNA polymerization that earned him the 1959 Nobel Prize in Physiology or Medicine.

Charles Clifton Richardson is an American biochemist and professor at Harvard University. Richardson received his undergraduate education at Duke University, where he majored in medicine. He received his M.D. at Duke Medical School in 1960. Richardson works as a professor at Harvard Medical School, and he served as editor/associate editor of the Annual Review of Biochemistry from 1972 to 2003. Richardson received the American Chemical Society Award in Biological Chemistry in 1968, as well as numerous other accolades.

References

  1. 1 2 Anon (2009). "Certificate of Election EC/2009/48: Roger D. Kornberg". London: Royal Society. Archived from the original on 2017-03-21.
  2. 1 2 "Roger D. Kornberg". people.embo.org.
  3. 1 2 Kornberg, Roger David (1972). The Diffusion of Phospholipids in Membranes (PhD thesis). Stanford University. OCLC   38611465. ProQuest   302673759.
  4. ↑ "The Nobel Prize in Chemistry 2006". NobelPrize.org. Retrieved 2020-06-01.
  5. ↑ "Roger Kornberg wins the 2006 Nobel Prize in Chemistry". Stanford University School of Medicine.
  6. ↑ "Press release: The Nobel Prize in Chemistry 2006". Royal Swedish Academy of Sciences.
  7. ↑ N, Kresge; Al., Et (2009). "The Decade-long Pursuit of a Reconstituted Yeast Transcription System: the Work of Roger D. Kornberg". J Biol Chem. 284 (43): e18-20. doi: 10.1016/S0021-9258(20)38209-0 . PMC   2785628 . PMID   19847957.
  8. ↑ BBC News report of Kornberg's Nobel Prize win
  9. ↑ Kornberg Nobel Prize lecture
  10. ↑ The Nobel Foundation 2006 prizes in Chemistry
  11. ↑ "Jewish Nobel Prize Winners in Chemistry". www.jinfo.org. Retrieved 2023-03-30.
  12. ↑ Vasmatkar, Pashupat; Kamaljit, Kaur (2019). Miracles in Biochemistry: The contribution of the Nobel laureates to the field of Biochemistry. India: Educreation Publishing. p. 99. ISBN   978-9388910743 . Retrieved 8 September 2021.
  13. ↑ Richardson, Charles C. (2 June 2015). "It Seems Like Only Yesterday". Annual Review of Biochemistry. 84 (1): 1–34. doi: 10.1146/annurev-biochem-060614-033850 . PMID   26034887.
  14. 1 2 Stoddart, Charlotte (1 March 2022). "Structural biology: How proteins got their close-up". Knowable Magazine. doi: 10.1146/knowable-022822-1 . Retrieved 25 March 2022.
  15. ↑ Kornberg, R. D. (1974). "Chromatin Structure: A Repeating Unit of Histones and DNA". Science. 184 (4139): 868–871. Bibcode:1974Sci...184..868K. doi:10.1126/science.184.4139.868. ISSN   0036-8075. PMID   4825889.
  16. ↑ Lorch, Yahli; LaPointe, Janice W.; Kornberg, Roger D. (1987). "Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones". Cell. 49 (7): 203–210. doi:10.1016/0092-8674(87)90561-7. PMID   3568125. S2CID   21270171.
  17. ↑ Capa, Nossa (2001). "Our Journal Cover". Jornal Brasileiro de Patologia e Medicina Laboratorial. 37 (4): 231. doi: 10.1590/S1676-24442001000400001 . Retrieved 8 September 2021.
  18. ↑ Kelleher, Raymond J.; Flanagan, Peter M.; Kornberg, Roger D. (1990). "A novel mediator between activator proteins and the RNA polymerase II transcription apparatus". Cell. 61 (7): 1209–1215. doi: 10.1016/0092-8674(90)90685-8 . ISSN   0092-8674. PMID   2163759. S2CID   4971987.
  19. ↑ "The Nobel Prize in Chemistry 2006". NobelPrize.org. Retrieved 2020-06-01.
  20. ↑ Cramer, P. (2001). "Structural Basis of Transcription: RNA Polymerase II at 2.8 Angstrom Resolution" (PDF). Science. 292 (5523): 1863–1876. Bibcode:2001Sci...292.1863C. doi:10.1126/science.1059493. hdl: 11858/00-001M-0000-0015-8729-F . ISSN   0036-8075. PMID   11313498. S2CID   4993438.
  21. ↑ Gnatt, A. L. (2001). "Structural Basis of Transcription: An RNA Polymerase II Elongation Complex at 3.3 A Resolution". Science. 292 (5523): 1876–1882. Bibcode:2001Sci...292.1876G. doi:10.1126/science.1059495. hdl: 11858/00-001M-0000-0015-8723-C . ISSN   0036-8075. PMID   11313499. S2CID   12379905.
  22. ↑ Bushnell, D. A. (2004). "Structural Basis of Transcription: An RNA Polymerase II-TFIIB Cocrystal at 4.5 Angstroms". Science. 303 (5660): 983–988. Bibcode:2004Sci...303..983B. doi:10.1126/science.1090838. ISSN   0036-8075. PMID   14963322. S2CID   36598301.
  23. ↑ A family story about life 2006
  24. ↑ Kornberg, RD; McConnell, HM (October 1971). "Lateral diffusion of phospholipids in a vesicle membrane". Proceedings of the National Academy of Sciences of the United States of America. 68 (10): 2564–8. Bibcode:1971PNAS...68.2564K. doi: 10.1073/pnas.68.10.2564 . PMC   389469 . PMID   4332815.
  25. ↑ Epand, Richard M.; Ruysschaert, Jean-Marie (September 25, 2017). The biophysics of cell membranes : biological consequences. Singapore: Springer. pp. 33–34. ISBN   9789811062438 . Retrieved 8 September 2021.
  26. ↑ Hartl, Franz-Ulrich (2001). "Roger D. Kornberg Felix Hoppe-Seyler Lecturer 2001". Biological Chemistry. 382 (8): 1101–2. doi:10.1515/BC.2001.139. ISSN   1431-6730. PMID   11592389. S2CID   41857405.
  27. ↑ "The 2005 Alfred P. Sloan, Jr. Laureate". Archived from the original on 2006-10-19. Retrieved 2006-10-04.
  28. ↑ The Official Site of Louisa Gross Horwitz Prize
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