Cells are the fundamental units of life, being the most irreducible entities that retain all of the basic properties of living things, such as metabolic activity and a means of reproducing. Just as whole organisms progress through their own version of a life cycle – birth, maturation, reproduction, aging and death – individual cells have a life cycle of their own, fittingly termed the cell cycle.
(Some living things, it must be noted, consist only of a single cell, making "life cycle" and "cell cycle" completely overlapping propositions for these organisms.)
Cells in complex organisms do not live nearly as long as the creatures in which they exist. The cell life cycle is generally more predictable and easier to separate into fairly distinct components than the life arc of a moderately complex animal.
These stages include interphase and the M phase, each of which includes a number of substages. The M phase encompasses mitosis, the process by which cells reproduce asexually to create new cells.
Phases of the Cell Cycle
Even the most formidable active volcanoes spend far more time dormant than they do erupting, but no one pays much attention to the quiescent periods. In a sense, cells are like this: mitosis is by far the most busy and dramatic part of the cell cycle, but the cell actually spends most of its time in interphase. This phase itself includes G1, S and G2 stages.
A newly created cell enters the first gap (G1) phase, during which all of the cell contents (e.g., mitochondria, endoplasmic reticulum, Golgi apparatus and other organelles) except for the chromosomes are duplicated.
In the subsequent synthesis (S) phase, all of the cell's chromosomes – in humans, there are 46 – are duplicated (or replicated, to use biochemistry parlance).
In the second gap (G2) phase, the cell performs a quality-control check on itself, scanning the replicated contents for errors and making any needed fixes. The cell then proceeds to the M phase.
- Some cells in tissues in which proliferation and turnover is low, such as liver, spend long periods of time in a phase labeled G0, with this "off-ramp" from the typical cycle occurring right after mitosis is complete.
What Happens Before M Phase
During interphase, the cell grows to the size it needs to in order to divide, making copies of its various elements in distinct steps along the way. The end of the G1 phase is signaled by a protein, marking what is called a G1 checkpoint.
A similar G2 checkpoint marks the start of the M phase. There is no S1 checkpoint, however. In some cells the S phase runs right into the M phase.
When the cell does not spend time checking its work in a programmed G2 phase, the event directly preceding the M phase is the DNA replication (the replication of chromosomes) in the S phase. Otherwise, a G2 phase of varying length occupies the point in the cell cycle right before mitosis begins.
Overview of Mitosis
Mitosis is a process that occurs in eukaryotic cells (e.g., plant cells, mammalian cells and those of other animals, protists and fungi) and results in the production of two daughter cells from one parent cell, with the daughter cells being genetically identical to the parent and to each other.
It is thus asexual, contrasting it with meiosis, a type of cell division that takes place in certain cells in the gonads and involves juggling and shuffling of genetic material. Its counterpart in the prokaryote world is binary fission. In most animal cells, the process takes about an hour – a small fraction of a typical cell's lifetime.
The word "mitosis" means "thread," as this describes the microscopic appearance of chromosomes that are preparing to divide and that have thus condensed into long, linear-appearing structures. Even under a powerful microscope, interphase chromosomes, which lie diffusely in the nucleus, are very difficult to visualize.
It is commonly believed that mitosis refers to the splitting into equal halves of the parent cell. This is not the case, as mitosis refers only to events within the nucleus involving chromosomes. Cell division as a whole is called cytokinesis, while nuclear division (including the nuclear envelope) is known as karyokinesis.
Phases of Mitosis
Classically, the four named stages of mitosis include, in the order they occur, prophase, metaphase, anaphase and telophase. Many sources include detailed description of a fifth phase, prometaphase, that is arguably distinct from both prophase and metaphase.
Each of these phases has its own intricate wonders, which will be detailed soon. But it is often helpful to mentally align every mitosis phase with a brief blurb about what it involves. For example:
- Prophase: Chromosome condensation occurs.
- Prometaphase: Spindles attach.
- Metaphase: Chromosomes align.
- Anaphase: Chromatids separate.
- Telophase: Membrane reforms.
Anyway, if one friend tells you that the M phase has four substages and someone else claims that it's five, chalk this up to likely differences in their ages (and thus when they learned about the M phase in school) and consider both of them right.
The appearance of condensed chromosomes marks the onset of prophase, in much the same way the formation of distinct clusters of chatting people marks the "official" start of a social gathering.
When chromatin condensation transforms the genetic material into fully formed chromosomes, the sister chromatids of each replicated chromosome can be seen joined at the centromere between them. The centromere is the spot where a kinetochore will eventually form on each chromatid.
Also in prophase, the two centrosomes, which were duplicated in interphase, start to move toward opposite sides, or poles, of the cell. In so doing they begin to assemble the mitotic spindle, which consists of spindle fibers made of microtubules that extend from the poles of the cell toward the center and become attached to the kinetochores (among other structures).
As you would likely predict, the spindle fibers are oriented parallel to each other and perpendicular to the eventual line of chromosome division.
Also, in many higher eukaryotes, the nuclear envelope is degraded under the action of protein kinase enzymes during this phase, and it will be rebuilt from scratch at the end of mitosis in telophase.
But in other organisms, the nuclear envelope is never formally disassembled. Instead, it is stretched out along with the cell in its entirely as the chromosomes separate and is neatly divided all at once.
Imagine yourself standing in a completely dark hallway, groping forward toward a bank of light switches that you know is there but cannot intuit the exact position of. But you really want a drink of water from the kitchen, so you are persistent.
This approximates the behavior of the spindle fibers as their ends "reach out" and grow toward chromosomes from both of the cell's poles. "Hoping" to connect to the kinetochores that serve as the spindle fibers' connection locus, they can be seen appearing to probe the cytoplasm, retract and probe some more until they finally strike their targets.
Before long, spindle fibers on each side of the cell have become attached to the kinetochore on the chromatid in each pair that happens to lie on the same side of the cell. There are no genetic implications of this randomness because each chromatid has the exact same DNA as its sister.
The spindle fibers then initiate a "tug of war" in an effort to ultimately balance their exertions in a way that leaves the centromeres of the chromosomes, and hence the chromosomes themselves, in a linear type of alignment.
At the onset of metaphase, nuclear envelope breakdown proceeds to completion, except, of course, in cells that don't lose their nuclear membranes at all. But the defining step of metaphase, which is typically very short, is that the chromosomes line up along the plane that will serve as the interface of chromosome division.
This tiny surface is called the metaphase plate, and, with the idea that the cell is like a very tiny sphere in mind, the position of this plate is along the equator of the cell.
It is possible for more than one spindle microtubule to attach to a given kinetochore from the same side, but at least one kinetochore microtubule is attached to each pole. After the microtubules have been engaged in their game of push-and-pull for long enough to arrive at a state of balanced tension, the chromosomes stop moving, and metaphase is over.
At this point, spindle fibers can wind up in two other places in the cell besides kinetochores. These may be polar microtubules (also called interpolar microtubules), which extend past the lined-up chromosomes and across the equator, almost to the opposite mitotic spindle origin; or astral microtubules, which reach from the spindle pole to the cell membrane on the same side.
Anaphase is the most visually striking component of M phase because it involves rapid chromosome movement when the replicated chromosomes split apart. This is accomplished by the sister chromatids in each duplicated, aligned chromosome set being drawn toward opposite poles of the cell by the spindle fibers.
This is done owing to the labors of the microtubules, but it is facilitated by the breakdown of the cohesin proteins that bind the kinetochore to the kinetochore fibers. In anaphase, the cell begins to stretch from a roughly spherical shape (or a circle, if you are looking at a cross-section) into a roughly ovoid shape (i.e., an ellipse).
Anaphase can be viewed as featuring anaphase A, in which the kinetochore spindle fibers pull the chromosomes apart as described, and anaphase B, in which the astral fibers pull the poles even farther from the equator and thus farther from each other, drawing the interpolar fibers past the chromosomes on the same side and lightly cajoling them along for the ride in the same direction.
Also, a contractile ring forms from actin proteins just beneath the plasma membrane in anaphase; this ring participates in the "squeezing" during cytokinesis that results in the cleavage of the whole cell.
At the start this part of the M phase, chromosomes in the form of daughter nuclei have reached opposite ends of the cell. The mitotic spindle, having completed its work, is disassembled; picture, say, some minuscule scaffolding built along the side of a tiny building to allow for construction being taken apart, beam by beam, and you get the idea.
This is really a clean-up step of M phase, analogous to the epilogue of a novel. The "plot" was resolved at the end of anaphase because the chromatids have gotten to where they were supposed to travel, but before the "characters" can move on, some housekeeping is required.
In telophase, the nuclear membrane is reassembled, and the chromosomes de-condense. This is not precisely like running the video of prophase in reverse, but it's close. In cytokinesis, the cell divides into two identical daughter cells, each of which prepares to enter the G1 phase and embark on a cell cycle of its own.
About the Author
Kevin Beck holds a bachelor's degree in physics with minors in math and chemistry from the University of Vermont. Formerly with ScienceBlogs.com and the editor of "Run Strong," he has written for Runner's World, Men's Fitness, Competitor, and a variety of other publications. More about Kevin and links to his professional work can be found at www.kemibe.com.