Pioneering Discoveries about the Cell Cycle by steepslope9876


									Pioneering Discoveries about the Cell Cycle

                   100 years ago, Emil von Behring –                 in the same manner in yeast cells,          Cell division – i. e. the multiplication
                   co-founder of modern immunolo-                    plants, animals and humans. Re-             of cells – is a fundamental process of
                   gy – received the first Nobel Prize               search on this subject had already          life. It has been known for more than
                   in medicine. The 2001 Prize was                   started in the 1970s, and today’s           100 years that cells multiply through
                   awarded on December 10, 2001                      discoveries – which have largely            division. An adult human being has
                   to three scientists all working                   increased our understanding of              approximately 100,000 billion cells,
                   in the field of cell reproduction,                genotype alterations in tumor               all originating from a single cell, the
                   albeit from different aspects.                    cells – now open up versatile               fertilized egg. During cell division,
                   Two Britons – Sir Paul Nurse and                  ways of (early) diagnosis and               cells responsible for various functions
                   Timothy Hunt – and the American                   treatment of cancer.                        originate from this single cell. Skin
                   Leland Hartwell were jointly                                                                  and nerve cells, but also cells of
                   honored for their pioneering,                                                                 organs like the liver and kidney,
                   fundamental discoveries of key                                                                perform specific functions which act
                   regulators and processes control-                                                             together to regulate the entire or-
                   ling the cell cycle. These are                                                                ganism. Almost all cells are continu-
                   molecules and processes that play                                                             ously dividing to replace dead cells. In
                   a key role in the growth and                                                                  eukaryotic organisms, the fundamen-
                   reproduction of cells and operate                                                             tal process of cell division was highly
                                                                                                                 conserved during evolution. Eukary-
                                                                                                                 otic cells have their chromosomes
Fig. 1:
Cell cycle                                       Cell with chromosomes in the nucleus                            located in a nucleus and separated
(Nobel e-Museum)                                                                                                 from the rest of the cell.
                                                                                                                     The cell cycle consists of several
                                                                                                                 clearly defined phases: growth of
                                                                                                                 cells with chromosomes in the nucle-
                                                                  G1                                             us (G1 phase), DNA synthesis and
                                     Cell division                                                               chromosome duplication (S phase),
                                                                                                                 preparation for cell division (G2
                                                                                                                 phase) and chromosome separation
                                                                                          DNA synthesis          and division into two daughter cells
                                                                                                                 (M phase). If the cells do not continu-
                           Mitosis           M              CDK                                                  ously divide, there is an additional
                                                                    cyclin              S                        resting stage (G0 phase) between
                                                                                                                 phases M and G1.
                                                                                    Chromosome duplication           Today, the findings already ob-
                          Chromosome separation                                                                  tained by the three prize winners in
                                                                                                                 the 1970s and 1980s are mainly used
                                                                                                                 in cancer research. The discovery of
                                                                  G2                                             key molecules in the cell cycle and
                                                                                                                 the description of their function are
                                                                                                                 the platform for preventive measures,
                                                                                                                 diagnostics and the treatment of
                                                     Cell with duplicated chromosomes                            malignant tumors. Future prevention
                                                                                                                 and treatment strategies can be

                                                                                                                 No            Innovation 11, Carl Zeiss, 2002
based on the knowledge of cell cycle                                                   cell division. Even minute defects          Fig. 2:
control.                                                                               in the cell division phases can             Function scheme
                                                                                                                                   of the cell cycle
    Although the findings were ob-                                                     contribute to the development of            (Nobel e-Museum)
tained with three different model or-                                                  tumors. And single defective cell
ganisms, they all fit together like a                                                  division genes may be carcinogenic.
puzzle and make a major contribu-
tion to understanding the cell cycle.
The Saccharomyces cerevisiae (Leland
Hartwell) and Schizosaccharomyces
pombe (Paul Nurse) yeasts con-
tributed to finding the “start” gene
and the CDK (cyclin-dependent
kinase) regulator component. The
cell division processes in the sea
urchin Arbacia (Timothy Hunt) led          identification of about 100 genes
to the discovery of the cyclin             specifically involved in cell cycle con-
mechanism.                                 trol. One of these genes, called
    Using genetic and molecular bio-       “start” gene, plays a major role at
logy methods in yeast cell experi-         the beginning of each cell cycle.                                                       Fig. 3:
ments, Sir Paul Nurse discovered           After irradiation experiments, the                                                      Nobel Prize Ceremony 2001.
                                                                                                                                   From left to right:
CDK, one of the key regulators of          checkpoint concept was introduced:                                                      Timothy Hunt,
the cell cycle. CDK activates further      the cell cycle is arrested when DNA                                                     Sir Paul Nurse,
decisive cell cycle proteins via chemi-    is damaged and a DNA repair                   Dr. Dieter Brocksch, Corporate Communi-   V. S. Naipaul,
                                                                                         cations/Technical Information             George A. Akerlof,
cal modification (phosphorylation),        mechanism is activated before the                                                       Michael Spencer
thus influencing and regulating the        cell cycle is continued. The concept                                                    (Photo: dpa)
cell division. Meanwhile, half a dozen     also includes controls ensuring a
different CDK molecules have been          correct order between the cell cycle
found in humans.                           phases.
    During cell division experiments          Basic processes in the cell cycle
using sea urchins, Timothy Hunt dis-       therefore include the function of
covered the central protein mole-          “duplicate hereditary material” on
cules, the so-called cyclins, which        the one hand and the process of
regulate the CDK key component.            “cell division” on the other. Before a
Cyclin degradation during cell divi-       cell can divide, it must grow, dupli-
sion is an important control mecha-        cate the chromosomes – the carriers
nism of the cell cycle. The levels of      of the hereditary material – and
cyclin vary periodically during the cell   equally distribute it to the two
cycle. Today we know around ten            daughter cells. The various cell cycle
different cyclins.                         phases must follow in the correct
    Using yeast cells as a model sys-      order and be precisely coordinated.
tem, Leland Hartwell studied the           The sum of all these single phases
genes controlling the cell cycle, the      coordinates the cell cycle. If cell cycle
so-called CDC (cell division cycle)        components are lost and/or mutated,
genes. Mutated genes led to the            this may often lead to uncontrolled

bel Prize
Innovation 11, Carl Zeiss, 2002                                                                                                                          17

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