Sunday, March 3, 2013

What is cell division?


Asexual vs. Sexual Reproduction

A cell’s genetic blueprint is encoded in genes written in the four-letter alphabet of DNA, which stands for the four nucleotides that make up the strands of DNA: guanine (G), adenine (A), thymine (T), and cytosine (C). Reproduction of this blueprint is an essential property of life. Prokaryotes (cells without nuclei) contain a single chromosome in the form of a circular double helix. They replicate their DNA and reproduce asexually by binary fission. . Eukaryotic cells, with two or more pairs of linear, homologous chromosomes in a nucleus, replicate their DNA and reproduce asexually by mitosis.. In sexual reproduction in higher organisms, special cells called germ cells are set aside to form gametes by meiosis.. During meiosis, the germ cells duplicate their chromosomes and separate the homologs into gametes. After mitosis, new cells have a copy of all of the chromosomes originally present in the parent cell; after meiosis, gametes (sperm or egg) contain only one of each homologous chromosome originally present in the parent cell. Though their chromosomal outcomes are quite different, the cellular events of mitosis and meiosis share many similar features, discussed below mostly in the context of mitosis. The focus here is on when cells replicate their DNA, when they physically divide, and how they partition duplicate sets of genetic information into progeny cells.




















Binary Fission vs. Meiosis, Mitosis, and Cytokinesis

During binary fission, which occurs in prokaryotic cells (cells that have no nucleus—primary bacteria), these small cells grow larger, become pinched in the middle, and eventually produce two new cells. A specific base sequence in the circular bacterial DNA molecule attaches to the cell membrane. When this sequence replicates during DNA synthesis it also attaches to the cell membrane, but on the opposite side of the cell. As the bacterial cell grows and divides, the two DNA attachment points become separated into the progeny cells, ensuring that each gets a copy of the original circular DNA molecule. DNA replication and cell division in prokaryotes are therefore simultaneous processes.


Mitosis (and meiosis) and cytokinesis, by contrast, are processes well separated in time from DNA replication. When first observed in the microscope in the 1880s, mitosis seemed to be a busy time in the life of a cell. During prophase (the initial phase of mitosis), nuclei seem to disintegrate in a matter of minutes at the same time that chromosomes take shape from nondescript nuclear substance. Spindle fibers form at opposite poles and grow toward the center of the cell. After about thirty minutes, cells are in metaphase. The spindle fibers extend across the cell, attaching to fully formed chromosomes lined up at the metaphase plate in the middle of the cell. Each chromosome is actually composed of two attached strands, or chromatids.


During anaphase the chromatids of each chromosome pull apart and move toward opposite poles of the cell. Telophase is characterized by the re-formation of nuclei around the chromosomes and the de-condensation of the chromosomes back to the shapeless substance now called chromatin..


Cytokinesis, meaning “cell movement,” begins during telophase, lasts about thirty minutes, and is the actual division of the parent cell into two cells, each of which gets one of the newly forming nuclei. The processes of mitosis and cytokinesis, which together typically last about one and a half hours, ensure that duplicated pairs of chromosomes are partitioned correctly into progeny cells.


Meiosis actually consists of two cell divisions, each progressing through prophase, metaphase, anaphase, and telophase. In the first division, homologous chromosomes with their chromatids are separated into progeny cells; in the second, chromatids are pulled apart into the cells that will become gametes. The result is to produce haploid eggs or sperm, rather than the diploid progeny with paired homologous chromosomes that result from mitosis.




The Cell Cycle

Early histologists studying mitosis noted that it often took cells about twenty hours to double, implying a long period between successive cell divisions. This period was called interphase, meaning simply “between” the mitotic phases. An interphase also separates the first meiotic division from a prior mitosis, though there is not always an interphase between the first and second meiotic divisions. One might have suspected that cells were not just biding their time between mitoses, but it was only in the middle of the twentieth century that the cell cycle was fully characterized, showing interphase to be a long and very productive time in the life of a cell.


In an elegant experiment, cultured cells were exposed to radioactive thymidine, a DNA precursor. After a few minutes, radioactive DNA was detected in the nuclei of some cells. However, no cells actually in mitosis were radioactive. This meant that DNA is not synthesized during mitosis. Radioactive condensed mitotic chromosomes were detected only four to five hours after cells had been exposed to the radioactive DNA precursor, suggesting that replication had ended four to five hours before the beginning of mitosis. Studies like this eventually revealed the five major intervals of the cell cycle: mitosis, cytokinesis, gap 1 (the G1 phase, a time of cell growth), DNA synthesis (the S phase of DNA synthesis), and gap 2 (the G2 phase, during which a cell continues growing and prepares for the next mitosis).


The overall length of the cell cycle differs for different cell types. Human neurons stop dividing shortly after birth, never to be replaced. Many other differentiated cells do not divide but are replaced periodically by stem cells that have the capacity to continue to divide and differentiate. Clearly, human genes must issue instructions telling cells when and when not to reproduce.




Controlling the Cell Cycle

Sometimes cells receive faulty instructions (for example, from environmental carcinogens) or respond inappropriately to otherwise normal commands from other cells. Cancer is a group of diseases in which normal regulation of the cell cycle has been lost and cells divide out of control. In research published in the 1970s, cells synchronized in mitosis were mixed with others synchronized in other phases of the cell cycle in the presence of polyethylene glycol (the main ingredient in automobile antifreeze). The antifreeze caused cells to fuse. Right after mixing, chromosomes and a mitotic spindle could be seen alongside an intact nucleus in the fused cells. Later, the intact nucleus broke down and chromosomes condensed. The conclusion from studies like this is that mitosing cells contain a substance that causes nuclear breakdown and chromosome condensation in nonmitosing cells. Similar results were seen when cells in meiosis were fused with nonmeiotic cells. When purified, the substances from meiotic and mitotic cells could be injected into nonmitosing cells, where they caused nuclear breakdown and the appearance of chromosomes from chromatin. The substance was called maturation (or mitosis) promoting factor (MPF). MPF contains one polypetide called cyclin and another called cyclin-dependent kinase (cdk). The kinase enzyme catalyzes transfer of a phosphate to other proteins; it is active only when bound to cyclin—hence the name. The kinase is always present in cells, while cyclin concentrations peak at mitosis and then fall. This explains why MPF activity is highest during mitosis and why mitotic cells fused to G1 cells, for example, can cause the G1 cell nucleus to disappear and chromosomes to emerge from chromatin.


Since the initial discovery of MPF, studies of eukaryotic cells, from yeast cells to human cells, have revealed many different cyclin-dependent kinases and other regulatory proteins that exert control at different checkpoints on the cell cycle, determining whether or not cells progress from one stage to another. Scientists remain ignorant of the exact causes of most cancers, but because of the compelling need to know, researchers are beginning to understand the normal controls on cellular reproduction and how those controls do not function correctly in cancer cells. In one 2012 study at Moffitt Cancer Center and the University of Florida, researchers identified a connection between the enzyme, tyrosine kinase (WEE1), and the modification of histone, a process that would benefit the growth of cancer cells. In another study conducted in conjunction with the Howard Hughes Medical Institute (2013), researchers examined the mechanisms that regulate gene expression in eukaryotes and identified regulatory pathways involved in cancer. These are only two examples of a multitude of studies whose ultimate goal is therapeutic intervention to prevent uninhibited cell growth.


A final word on the cyclin-dependent protein kinase: This enzyme is one of a large number of kinases that participate in regulating cell chemistry and behavior in response to many extracellular signals (such as hormones). The phosphorylation of cellular proteins has emerged as a major theme in the regulation of many cellular activities, including cell division.




Key terms




asexual reproduction


:

a form of reproduction wherein an organism’s cell DNA doubles and is distributed equally to progeny cells





binary fission


:

cell division in prokaryotes in which the plasma membrane and cell wall grow inward and divide the cell in two




chromatid

:

one-half of a replicated chromosome





chromatin


:

the material that makes up chromosomes; a complex of fibers composed of DNA, histone proteins, and nonhistone proteins





chromosome


:

a self-replicating structure, consisting of DNA and protein, that contains part of the nuclear genome of a eukaryote; also used to describe the DNA molecules constituting the prokaryotic genome




cyclin-dependent kinases (cdk’s)

:

proteins that regulate progress through the eukaryotic cell cycle




cyclins

:

proteins whose levels rise and fall during the cell cycle





cytokinesis


:

movements of and in a cell resulting in the division of one eukaryotic cell into two





DNA replication


:

synthesis of new DNA strands complementary to parental DNA




genome

:

the species-specific, total DNA content of a single cell





meiosis


:

a type of cell division that leads to production of gametes (sperm and egg) during sexual reproduction





mitosis


:

nuclear division, a process of allotting a complete set of chromosomes to two daughter nuclei




phases of mitosis and meiosis

:

periods—including prophase, metaphase, anaphase, and telophase—characterized by specific chromosomal events during cell division




phases of the cell cycle

:

mitosis, cytokinesis, G1 (gap 1), S (DNA synthesis), and G2 (gap 2)




phosphorylation

:

a chemical reaction in which a phosphate is added to a molecule, common in the control of cell activity, including the regulation of passage through different stages of the cell cycle





Bibliography


Alberts, Bruce, et al. Molecular Biology of the Cell. 5th ed. New York: Garland Science, 2008.



Genetics Home Reference. "How Do Cells Divide?" Genetics Home Reference. US Natl. Lib. of Medicine, 2014. Web. 1 Aug. 2014.



Green, Michael. "Eukaryotic Gene Regulation and Cancer Molecular Biology." Howard Hughes Medical Inst.. Howard Hughes Medical Inst., 8 Oct. 2013. Web. 6 Aug. 2014.



Karp, Gerald. Cell and Molecular Biology: Concepts and Experiments. 7th ed. Hoboken: Wiley , 2013. Print..



Knoblich, Juergen A. "Asymmetric Cell Division: Recent Developments and Their Implications for Tumor Biology." Nature Reviews Molecular Cell Biology 11.12 (2010): 849–60. Print.



Morgan, David O. The Cell Cycle: Principles of Control. London: New Science P in association with Oxford UP , 2007. Print.



Murray, A. W., and Tim Hunt. The Cell Cycle: An Introduction. New York: W. H. Freeman, 1993.



Reece, Jane B., et al. Campbell Biology. 9th ed. San Francisco: Cummings–Pearson, 2011. Print.

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