Cell cycle

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The cell cycle is the sequence of different phases of activity between the divisions of eukaryotic cells . Since the DNA content of a cell or a cell nucleus is halved during division ( mitosis ), it must be doubled again before the next division. These two processes are referred to as M-phase and S-phase (of synthesis ). Between them are so-called Gap phases (engl. Gap ): G 1 and G 2 .

Phases

Individual phases of mitosis

After the mother cell divides, the daughter cells begin the interphase . In this phase between two mitoses, the individual chromosomes cannot be recognized as individual units even after staining. The gene activity controls the metabolism of the growing cell. Your cell nucleus develops at least one nucleolus . Because of the ribosomal RNA content , nucleoli are a prerequisite and an indication of cellular metabolism. An important process during interphase is the duplication of chromosomes.

Cell cycle scheme. M = mitotic phase. The following interphase consists of G 1 , S and G 2 . A cell can change from G 1 to the G 0 state

This happens during the synthesis or S phase. It is preceded by the G 1 phase. Correspondingly, the S phase is followed by the G 2 phase.

G 1 phase
The designation G 1 phase comes from gap , as this is the period between nucleus division and DNA synthesis. In this (postmitotic or presynthetic) phase, cell components ( cytoplasm , cell organelles ) are supplemented. The production of mRNAs for histones and replication enzymes ( DNA polymerases , ligases ) is required for the upcoming S-phase. For the same reason, the supply of deoxyribonucleoside triphosphates increases. In the cytoplasm of animal cells, the two centrioles separate from one another.
Each chromosome consists of only one chromatid or one DNA helix. The DNA content of the G 1 cell can be determined as 2 C by means of DNA cytometry . The C value stands for the size of the (haploid) genome of an organism.
  • Cells switch from the G 1 phase to the G 0 phase when they are no longer supposed to multiply ( cells at rest ). These can be cells that will never divide again, such as nerve cells and muscle cells of the striated muscles. Other cell types remain in G 0 for weeks or months after their differentiation , but in the event of special events such as injury or cell loss they can return to the G 1 state and subsequently divide. Examples are liver cells ( hepatocytes ) and lymphocytes .
S phase
stands for synthesis phase, because of the duplication of DNA in the cell nucleus. Triggered by genetic signals begins in each chromosome in several origins , the replication , the doubling of the DNA helix. Corresponding amounts of new histones reach the cell nucleus from the cytoplasm, which pack the replicated DNA. The centrioles also double.
The S-phase ends as soon as the DNA doubling is complete and each chromosome consists of two chromatids. The amount of DNA increases from 2 ° C to 4 ° C in this phase .
G 2 phase
In this (postsynthetic or premitotic) interval, RNA molecules and proteins specific to cell division are synthesized in order to prepare the subsequent mitosis. The endoplasmic reticulum is melted down. In tissues, the contacts to the neighboring cells dissolve; the cell becomes rounded and enlarged by absorbing fluid.
M phase
or mitosis phase: this is where the division of chromosomes (mitosis), the cell nucleus (karyokinesis) and the cell (cytokinesis) into two parts takes place. During mitosis, the following follow one another: prophase , prometaphase , metaphase , anaphase and telophase , cell division usually begins parallel to the last phases of mitosis. Cell division halves the amount of DNA from 4 C to 2 C again .
  • If cells do not divide and the amount of DNA is further doubled, it is called endoreplication . This is used in some high-performance cells for increased protein biosynthesis.

Duration

The duration of the cell cycle, i.e. H. the time between successive cell divisions can be very different:

  • It is one of the shortest during the cleavage divisions in the earliest stage of development of animal embryos , in which a large cytoplasm mass is divided into many cells within a short time and a cycle lasts just under 10 minutes. The G 1 and G 2 phases are almost completely eliminated , and the S and M phases are accelerated.
  • It lasts longest in cells that temporarily or permanently no longer divide. In these no more replication takes place after the last mitosis, the cell remains in the G 0 phase.
Duration of the division phases according to
Cell type Duration of the phase
G 1 S. G 2 M. total
Slime mold ( Physarum polycephalum ) very short 02 h, 0 04 h 00.7 h 06.7 h
Bean ( Vicia faba ) meristem of the root tip 0004 h 09 h 03.5 h 02 h 18.5 h
Mouse ( Mus musculus ) tumor cells in culture 0010 h 09 h 04 h 01 h 24 hours
Human ( Homo sapiens ) tumor cells in culture 0008 h 06 h 04.5 h 01 h 19.5 h

regulation

External factors

The factors that regulate the cell cycle include cell size and the supply of nutrients. The presence or absence of neighboring cells also plays a role. Animal cells that have grown densely no longer divide; they pass into the G 0 stage. Furthermore, the growth factors determined for them control the course of the cycle in tissues .

Certain chemicals can hold cells growing in culture in a certain cell cycle stage and thus synchronize the cells of a culture. For example, deoxythymidine and aphidicolin are used, which keep the cells in the S-phase.

Internal factors and control points

The duration and sequence of the phases are monitored at checkpoints . They ensure that the next step in the cell cycle does not take place until the previous one has been completed. At the checkpoints, it is possible to simply interrupt the cell cycle (arrest) or to initiate programmed cell death ( apoptosis ).

There are special cell cycle proteins such as CDKs ( cycline dependent kinases ) and cyclins . At certain points in time in the cycle, these proteins are increasingly expressed until their concentration reaches a maximum. This maximum is believed to be the control point. After that, the cyclins are quickly broken down. CDKs and the associated cyclins form complexes whose activation (dephosphorylation of Thr14 and Tyr15 by cdc25 ) or deactivation is controlled, among other things, by growth factors and proto-oncogenes . The CDKs phosphorylate and activate a number of other proteins specifically and thus control the cell cycle.

An example of a checkpoint is

  • Checkpoint for DNA damage : If nucleotides are missing , if the DNA metabolism is otherwise disturbed, or if the DNA is damaged by radiation or chemical substances ( mutagens ), this generates a signal ( p53 , which activates p21 ). It causes the cell to remain in one of the two G-phases or in the S-phase. If it hits the S phase, the DNA synthesis is stopped by inhibiting the cyclin D / CDK4 / 6 complex, the cyclin E / CDK2 complex and the delta subunit of DNA polymerase. Repair genes are activated to repair the DNA damage.
  • Control point of the spindle formation: The separation of the chromatids in the anaphase of mitosis is prevented until all centromeres ( kinetochores ) are connected to the transport fibers of the spindle apparatus and the chromosomes are arranged next to one another in the equatorial plate.

Initiation of cell division

Nuclear division (mitosis) and finally cell division is initiated in eukaryotes by the mitosis promoting factor ( MPF ). The protein complex MPF consists of the cyclin-dependent kinase “ CDK1 ” and “ cyclin B ”. In the active form, the complex phosphorylates various proteins - such as histone H1  - and starts the prophase of mitosis. The activated histones cause the DNA to spiral, the so-called " supercoiling ", which is one of the basic requirements for the beginning of the nucleus division.

Cell cycle and cancer

The cell cycle of neoplastic cells ( cancer cells ) is no longer controlled by the organism. These cells divide autonomously. The duration of a cell cycle is different compared to normal cells.

The discovery of the cell cycle allowed a deeper insight into the development of cancer. Dysregulations in the cell cycle can lead to uncontrolled cell and thus tissue growth. Important regulatory proteins (e.g. p53 ) are lost through mutation or are excessively expressed.

Nobel Prize in Medicine

Scientists Leland H. Hartwell ( USA ), Tim Hunt ( UK ) and Paul M. Nurse (UK) received the 2001 Nobel Prize for Medicine for their discoveries on how to control the cell cycle .

Web links

Commons : Cell cycle  - collection of images, videos and audio files
  • Lexicon of biology: cell cycle . Spectrum, Heidelberg 1999.

Individual evidence

  1. ^ H Lundegård: Fixation, staining and nomenclature of nuclear structures, a contribution to the theory of cytological methodology. In: Archives for Microscopic Anatomy 80: 223–273, 1912.
  2. ↑ a b A Howard, SR Pelc: Synthesis of deoxyribonucleic acid in normal and irradiated cells and its relation to chromosome breakage. In: Heredity , 6, 1953, pp. 261-273.
  3. ↑ Swift Hewson Hoyt: The constancy of desoxyribose nucleic acid in plant nuclei. In: Proceedings of the National Academy of Sciences USA , 36, 1950, pp. 643-654.
  4. ↑ a b Renate Huch (Hrsg.), Klaus D. Jürgens (Hrsg.): Mensch Body Disease , 6th Edition, 2011, Urban & Fischer Verlag / Elsevier, ISBN 978-3-437-26792-5 , p. 34 .
  5. ↑ Joel A Huberman, Arthur D Riggs: On the mechanism of DNA replication in mammalian chromosomes. In: Journal of Molecular Biology , 32, 1968, pp. 327-341.
  6. ↑ Katharina Munk (ed.): Basic studies in biology - biochemistry, cell biology, ecology, evolution. Spektrum Akademischer Verlag, Heidelberg / Berlin 2000, ISBN 3-8274-0910-1 , pp. 13-14.
  7. ↑ Katharina Munk (ed.): Basic studies in biology - biochemistry, cell biology, ecology, evolution. Spektrum Akademischer Verlag, Heidelberg Berlin 2000, ISBN 3-8274-0910-1 , pp. 13-15.
  8. ↑ Pedrali-Noy, G. et al. : Synchronization of HeLa cell cultures by inhibition of DNA polymerase alpha with aphidicolin , in: Nucleic Acids Res. 1980 8 (2): 377-387; PMID 6775308 , PMC 327273 (free full text)
  9. ↑ Hamid Emminger, Christian Benz: Physikum exact: The entire examination knowledge for the 1. Äp. 4th edition, Georg Thieme Verlag, 2005, ISBN 978-3-13-107034-0 , p. 18
  10. ^ Nobel Prize for Medicine and Physiology 2001