10.2: El ciclo celular

Habilidades para Desarrollar

• Describir las tres etapas de la interfase
• Discutir el comportamiento de los cromosomas durante la cariocinesis
• Explicar cómo se divide el contenido citoplásmico durante la citocinesis
• Definir la fase G ₀ quiescente

El ciclo celular es una serie ordenada de eventos que involucran crecimiento celular y división celular que produce dos nuevas células hijas. Las células en el camino a la división celular proceden a través de una serie de etapas de crecimiento, replicación de ADN y división cronometradas con precisión y cuidadosamente reguladas que producen dos células idénticas (clonadas). El ciclo celular tiene dos fases principales: la interfase y la fase mitótica (Figura\(\PageIndex{1}\)). Durante la interfase, la célula crece y el ADN se replica. Durante la fase mitótica, el ADN replicado y el contenido citoplásmico se separan, y la célula se divide.

Figura\(\PageIndex{1}\): El ciclo celular consiste en la interfase y la fase mitótica. Durante la interfase, la célula crece y el ADN nuclear se duplica. A la interfase le sigue la fase mitótica. Durante la fase mitótica, los cromosomas duplicados son segregados y distribuidos en núcleos hijos. Por lo general, el citoplasma también se divide, dando como resultado dos células hijas.

Interfase

Durante la interfase, la célula se somete a procesos de crecimiento normales mientras que también se prepara para la división celular. Para que una célula pase de la interfase a la fase mitótica, se deben cumplir muchas condiciones internas y externas. Las tres etapas de interfase se denominan G ₁, S y G ₂.

Fase G ₁ (Primer Gap)

La primera etapa de interfase se denomina fase G ₁ (primer hueco) porque, desde un aspecto microscópico, es visible poco cambio. Sin embargo, durante la etapa G ₁, la célula es bastante activa a nivel bioquímico. La célula está acumulando los bloques de construcción del ADN cromosómico y las proteínas asociadas, así como acumulando suficientes reservas de energía para completar la tarea de replicar cada cromosoma en el núcleo.

Fase S (Síntesis de ADN)

Durante la interfase, el ADN nuclear permanece en una configuración de cromatina semicondensada. En la fase S, la replicación del ADN puede proceder a través de los mecanismos que dan como resultado la formación de pares idénticos de moléculas de ADN —cromátidas hermanas— que están firmemente unidas a la región centromérica. El centrosoma se duplica durante la fase S. Los dos centrosomas darán lugar al huso mitótico, el aparato que orquesta el movimiento de los cromosomas durante la mitosis. En el centro de cada célula animal, los centrosomas de las células animales están asociados con un par de objetos similares a barras, los centriolos, que están en ángulo recto entre sí. Los centriolos ayudan a organizar la división celular. Los centriolos no están presentes en los centrosomas de otras especies eucariotas, como las plantas y la mayoría de los hongos.

Fase G ₂ (Segundo Gap)

En la fase G ₂, la célula repone sus reservas de energía y sintetiza las proteínas necesarias para la manipulación cromosómica. Algunos orgánulos celulares se duplican, y el citoesqueleto se desmantela para proporcionar recursos para la fase mitótica. Puede haber crecimiento celular adicional durante G ₂. Los preparativos finales para la fase mitótica deben completarse antes de que la célula pueda ingresar a la primera etapa de la mitosis.

La fase mitótica

La fase mitótica es un proceso multietapa durante el cual los cromosomas duplicados se alinean, separan y se mueven en dos nuevas células hijas idénticas. La primera porción de la fase mitótica se llama cariocinesis, o división nuclear. La segunda porción de la fase mitótica, llamada citocinesis, es la separación física de los componentes citoplásmicos en las dos células hijas.

Enlace al aprendizaje

Revisitar los estadios de la mitosis en este sitio.

Caricinesis (Mitosis)

La cariokinesis, también conocida como mitosis, se divide en una serie de fases —profase, prometafase, metafase, anafase y telofase— que dan como resultado la división del núcleo celular (Figura\(\PageIndex{2}\)). Karyokinesis is also called mitosis.

Figure \(\PageIndex{2}\): Karyokinesis (or mitosis) is divided into five stages—prophase, prometaphase, metaphase, anaphase, and telophase. The pictures at the bottom were taken by fluorescence microscopy (hence, the black background) of cells artificially stained by fluorescent dyes: blue fluorescence indicates DNA (chromosomes) and green fluorescence indicates microtubules (spindle apparatus). (credit “mitosis drawings”: modification of work by Mariana Ruiz Villareal; credit “micrographs”: modification of work by Roy van Heesbeen; credit “cytokinesis micrograph”: Wadsworth Center/New York State Department of Health; scale-bar data from Matt Russell)

Exercise \(\PageIndex{1}\)

Which of the following is the correct order of events in mitosis?

1. Sister chromatids line up at the metaphase plate. The kinetochore becomes attached to the mitotic spindle. The nucleus reforms and the cell divides. Cohesin proteins break down and the sister chromatids separate.
2. The kinetochore becomes attached to the mitotic spindle. Cohesin proteins break down and the sister chromatids separate. Sister chromatids line up at the metaphase plate. The nucleus reforms and the cell divides.
3. The kinetochore becomes attached to the cohesin proteins. Sister chromatids line up at the metaphase plate. The kinetochore breaks down and the sister chromatids separate. The nucleus reforms and the cell divides.
4. The kinetochore becomes attached to the mitotic spindle. Sister chromatids line up at the metaphase plate. Cohesin proteins break down and the sister chromatids separate. The nucleus reforms and the cell divides.

Answer

D. The kinetochore becomes attached to the mitotic spindle. Sister chromatids line up at the metaphase plate. Cohesin proteins break down and the sister chromatids separate. The nucleus reforms and the cell divides.

During prophase, the “first phase,” the nuclear envelope starts to dissociate into small vesicles, and the membranous organelles (such as the Golgi complex or Golgi apparatus, and endoplasmic reticulum), fragment and disperse toward the periphery of the cell. The nucleolus disappears (disperses). The centrosomes begin to move to opposite poles of the cell. Microtubules that will form the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly with the aid of condensin proteins and become visible under a light microscope.

During prometaphase, the “first change phase,” many processes that were begun in prophase continue to advance. The remnants of the nuclear envelope fragment. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and discrete. Each sister chromatid develops a protein structure called a kinetochore in the centromeric region (Figure \(\PageIndex{3}\)). The proteins of the kinetochore attract and bind mitotic spindle microtubules. As the spindle microtubules extend from the centrosomes, some of these microtubules come into contact with and firmly bind to the kinetochores. Once a mitotic fiber attaches to a chromosome, the chromosome will be oriented until the kinetochores of sister chromatids face the opposite poles. Eventually, all the sister chromatids will be attached via their kinetochores to microtubules from opposing poles. Spindle microtubules that do not engage the chromosomes are called polar microtubules. These microtubules overlap each other midway between the two poles and contribute to cell elongation. Astral microtubules are located near the poles, aid in spindle orientation, and are required for the regulation of mitosis.

Figure \(\PageIndex{3}\): During prometaphase, mitotic spindle microtubules from opposite poles attach to each sister chromatid at the kinetochore. In anaphase, the connection between the sister chromatids breaks down, and the microtubules pull the chromosomes toward opposite poles.

During metaphase, the “change phase,” all the chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other by cohesin proteins. At this time, the chromosomes are maximally condensed.

During anaphase, the “upward phase,” the cohesin proteins degrade, and the sister chromatids separate at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule is attached. The cell becomes visibly elongated (oval shaped) as the polar microtubules slide against each other at the metaphase plate where they overlap.

During telophase, the “distance phase,” the chromosomes reach the opposite poles and begin to decondense (unravel), relaxing into a chromatin configuration. The mitotic spindles are depolymerized into tubulin monomers that will be used to assemble cytoskeletal components for each daughter cell. Nuclear envelopes form around the chromosomes, and nucleosomes appear within the nuclear area.

Cytokinesis

Cytokinesis, or “cell motion,” is the second main stage of the mitotic phase during which cell division is completed via the physical separation of the cytoplasmic components into two daughter cells. Division is not complete until the cell components have been apportioned and completely separated into the two daughter cells. Although the stages of mitosis are similar for most eukaryotes, the process of cytokinesis is quite different for eukaryotes that have cell walls, such as plant cells.

In cells such as animal cells that lack cell walls, cytokinesis follows the onset of anaphase. A contractile ring composed of actin filaments forms just inside the plasma membrane at the former metaphase plate. The actin filaments pull the equator of the cell inward, forming a fissure. This fissure, or “crack,” is called the cleavage furrow. The furrow deepens as the actin ring contracts, and eventually the membrane is cleaved in two (Figure \(\PageIndex{4}\)).

In plant cells, a new cell wall must form between the daughter cells. During interphase, the Golgi apparatus accumulates enzymes, structural proteins, and glucose molecules prior to breaking into vesicles and dispersing throughout the dividing cell. During telophase, these Golgi vesicles are transported on microtubules to form a phragmoplast (a vesicular structure) at the metaphase plate. There, the vesicles fuse and coalesce from the center toward the cell walls; this structure is called a cell plate. As more vesicles fuse, the cell plate enlarges until it merges with the cell walls at the periphery of the cell. Enzymes use the glucose that has accumulated between the membrane layers to build a new cell wall. The Golgi membranes become parts of the plasma membrane on either side of the new cell wall (Figure \(\PageIndex{4}\)).

Figure \(\PageIndex{4}\): During cytokinesis in animal cells, a ring of actin filaments forms at the metaphase plate. The ring contracts, forming a cleavage furrow, which divides the cell in two. In plant cells, Golgi vesicles coalesce at the former metaphase plate, forming a phragmoplast. A cell plate formed by the fusion of the vesicles of the phragmoplast grows from the center toward the cell walls, and the membranes of the vesicles fuse to form a plasma membrane that divides the cell in two.

G₀ Phase

Not all cells adhere to the classic cell cycle pattern in which a newly formed daughter cell immediately enters the preparatory phases of interphase, closely followed by the mitotic phase. Cells in G₀ phase are not actively preparing to divide. The cell is in a quiescent (inactive) stage that occurs when cells exit the cell cycle. Some cells enter G₀ temporarily until an external signal triggers the onset of G₁. Other cells that never or rarely divide, such as mature cardiac muscle and nerve cells, remain in G₀ permanently.

Scientific Method Connection: Determine the Time Spent in Cell Cycle Stages

Problem: How long does a cell spend in interphase compared to each stage of mitosis?

Background: A prepared microscope slide of blastula cross-sections will show cells arrested in various stages of the cell cycle. It is not visually possible to separate the stages of interphase from each other, but the mitotic stages are readily identifiable. If 100 cells are examined, the number of cells in each identifiable cell cycle stage will give an estimate of the time it takes for the cell to complete that stage.

Problem Statement: Given the events included in all of interphase and those that take place in each stage of mitosis, estimate the length of each stage based on a 24-hour cell cycle. Before proceeding, state your hypothesis.

Test your hypothesis: Test your hypothesis by doing the following:

1. Place a fixed and stained microscope slide of whitefish blastula cross-sections under the scanning objective of a light microscope.
2. Locate and focus on one of the sections using the scanning objective of your microscope. Notice that the section is a circle composed of dozens of closely packed individual cells.
3. Switch to the low-power objective and refocus. With this objective, individual cells are visible.
4. Switch to the high-power objective and slowly move the slide left to right, and up and down to view all the cells in the section (Figure \(\PageIndex{5}\)). As you scan, you will notice that most of the cells are not undergoing mitosis but are in the interphase period of the cell cycle.

   

   (a)

   

   (b)

   Figure \(\PageIndex{5}\): Slowly scan whitefish blastula cells with the high-power objective as illustrated in image (a) to identify their mitotic stage. (b) A microscopic image of the scanned cells is shown. (credit “micrograph”: modification of work by Linda Flora; scale-bar data from Matt Russell)

5. Practice identifying the various stages of the cell cycle, using the drawings of the stages as a guide (Figure \(\PageIndex{2}\)).

6. Once you are confident about your identification, begin to record the stage of each cell you encounter as you scan left to right, and top to bottom across the blastula section.

7. Keep a tally of your observations and stop when you reach 100 cells identified.

8. The larger the sample size (total number of cells counted), the more accurate the results. If possible, gather and record group data prior to calculating percentages and making estimates.

Record your observations: Make a table similar to the Table \(\PageIndex{1}\) in which you record your observations.

Table \(\PageIndex{1}\): Results of cell stage identification.

Phase or Stage	Individual Totals	Group Totals	Percent
Interphase
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis
Totals	100	100	100 percent

Analyze your data/report your results: To find the length of time whitefish blastula cells spend in each stage, multiply the percent (recorded as a decimal) by 24 hours. Make a table similar to the Table \(\PageIndex{2}\) to illustrate your data.

Table \(\PageIndex{2}\): Estimate of cell stage length.

Phase or Stage	Percent (as Decimal)	Time in Hours
Interphase
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis

Draw a conclusion: Did your results support your estimated times? Were any of the outcomes unexpected? If so, discuss which events in that stage might contribute to the calculated time.

Summary

The cell cycle is an orderly sequence of events. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages. In eukaryotes, the cell cycle consists of a long preparatory period, called interphase. Interphase is divided into G₁, S, and G₂ phases. The mitotic phase begins with karyokinesis (mitosis), which consists of five stages: prophase, prometaphase, metaphase, anaphase, and telophase. The final stage of the mitotic phase is cytokinesis, during which the cytoplasmic components of the daughter cells are separated either by an actin ring (animal cells) or by cell plate formation (plant cells).

Glossary

anaphase

stage of mitosis during which sister chromatids are separated from each other

cell cycle

ordered series of events involving cell growth and cell division that produces two new daughter cells

cell plate

structure formed during plant cell cytokinesis by Golgi vesicles, forming a temporary structure (phragmoplast) and fusing at the metaphase plate; ultimately leads to the formation of cell walls that separate the two daughter cells

centriole

rod-like structure constructed of microtubules at the center of each animal cell centrosome

cleavage furrow

constriction formed by an actin ring during cytokinesis in animal cells that leads to cytoplasmic division

condensin

proteins that help sister chromatids coil during prophase

cytokinesis

division of the cytoplasm following mitosis that forms two daughter cells.

G₀ phase

distinct from the G₁ phase of interphase; a cell in G₀ is not preparing to divide

G₁ phase

(also, first gap) first phase of interphase centered on cell growth during mitosis

G₂ phase

(also, second gap) third phase of interphase during which the cell undergoes final preparations for mitosis

interphase

period of the cell cycle leading up to mitosis; includes G₁, S, and G₂ phases (the interim period between two consecutive cell divisions

karyokinesis

mitotic nuclear division

kinetochore

protein structure associated with the centromere of each sister chromatid that attracts and binds spindle microtubules during prometaphase

metaphase plate

equatorial plane midway between the two poles of a cell where the chromosomes align during metaphase

metaphase

stage of mitosis during which chromosomes are aligned at the metaphase plate

mitosis

(also, karyokinesis) period of the cell cycle during which the duplicated chromosomes are separated into identical nuclei; includes prophase, prometaphase, metaphase, anaphase, and telophase

mitotic phase

period of the cell cycle during which duplicated chromosomes are distributed into two nuclei and cytoplasmic contents are divided; includes karyokinesis (mitosis) and cytokinesis

mitotic spindle

apparatus composed of microtubules that orchestrates the movement of chromosomes during mitosis

prometaphase

stage of mitosis during which the nuclear membrane breaks down and mitotic spindle fibers attach to kinetochores

prophase

stage of mitosis during which chromosomes condense and the mitotic spindle begins to form

quiescent

refers to a cell that is performing normal cell functions and has not initiated preparations for cell division

S phase

second, or synthesis, stage of interphase during which DNA replication occurs

telophase

stage of mitosis during which chromosomes arrive at opposite poles, decondense, and are surrounded by a new nuclear envelope