1.4: Mitosis

Learning Objectives

• List and describe the key events that occur during the cell cycle and mitosis.
• Describe the movement of chromosomes and chromatids during mitosis and the role of microtubules.
• Determine the chromosome content of cells during various stages given information about the n or 2n number of the cell. 

 

Copying and Dividing Chromosomes is a Cellular Challenge

 

Figure \(\PageIndex{1}\): DNA released from human chromosome. It shows a bit (no more than 3%) of the single molecule of DNA released from a single human chromosome. (The chromosome was treated to remove its histones). Remembering that this is 3% of the DNA of only one of the 46 chromosomes in the human diploid cell, you can appreciate the problem faced by the cell of how to separate without error these great lengths of DNA without creating horrible tangles. (courtesy J. R. Paulson and U. C. Laemmli)

 

The solution to this challenge is:

1. Duplicate each chromosome during the S phase of the cell cycle.
2. This produces dyads, each made up of 2 identical sister chromatids. These are held together by a ring of proteins called cohesin.
3. Condense the chromosomes into a compact form. This requires ATP and protein complexes called condensins.
4. Separate the sister chromatids and
5. Distribute these equally between the two daughter cells

 

Cell Cycle

The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produces two identical (clone) cells. The cell cycle has two major phases: interphase and the mitotic phase. During interphase, the cell grows and DNA is replicated. During the mitotic phase, the replicated DNA and cytoplasmic contents are separated, and the cell divides.

Figure \(\PageIndex{2}\): The cell cycle consists of interphase and the mitotic phase. During interphase, the cell grows and the nuclear DNA is duplicated. Interphase is followed by the mitotic phase. During the mitotic phase, the duplicated chromosomes are segregated and distributed into daughter nuclei. The cytoplasm is usually divided as well, resulting in two daughter cells. (OpenStaxCNX)

The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produces two identical (clone) cells. The cell cycle has two major phases: interphase and the mitotic phase. During interphase, the cell grows and DNA is replicated. During the mitotic phase, the replicated DNA and cytoplasmic contents are separated, and the cell divides.

 

Interphase

During interphase, the cell undergoes normal growth processes while also preparing for cell division. In order for a cell to move from interphase into the mitotic phase, many internal and external conditions must be met. The three stages of interphase are called G₁, S, and G₂.

Video \(\PageIndex{1}\): Interphase | Cells | MCAT | Khan Academy

 

G₁ Phase (First Gap)

The first stage of interphase is called the G₁ phase (first gap) because, from a microscopic aspect, little change is visible. However, during the G₁ stage, the cell is quite active at the biochemical level. The cell is accumulating the building blocks of chromosomal DNA and the associated proteins as well as accumulating sufficient energy reserves to complete the task of replicating each chromosome in the nucleus.

S Phase (Synthesis of DNA)

Throughout interphase, nuclear DNA remains in a semi-condensed chromatin configuration. In the S phase, DNA replication can proceed through the mechanisms that result in the formation of identical pairs of DNA molecules—sister chromatids—that are firmly attached to the centromeric region via proteins called cohesins.

Counting chromosomes and chromatids

Note that the two sister chromatids, which are held together by cohesin proteins, are still counted as a single chromosome until they are split apart during mitosis.

The centrosome is also duplicated during the S phase. The two centrosomes will give rise to the mitotic spindle, the apparatus that orchestrates the movement of chromosomes during mitosis. At the center of each animal cell, the centrosomes of animal cells are associated with a pair of rod-like objects, the centrioles, which are at right angles to each other. Centrioles help organize cell division. Centrioles are not present in the centrosomes of other eukaryotic species, such as plants and most fungi.

G₂ Phase (Second Gap)

In the G₂ phase, the cell replenishes its energy stores and synthesizes proteins necessary for chromosome manipulation. Some cell organelles are duplicated, and the cytoskeleton is dismantled to provide resources for the mitotic phase. There may be additional cell growth during G₂. The final preparations for the mitotic phase must be completed before the cell is able to enter the first stage of mitosis.

What's in the gaps?

What specific types of proteins does the cell need to make during G₁? During G₂?

 

Mitosis

The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and move into two new, identical daughter cells. The first portion of the mitotic phase is called karyokinesis, or nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into the two daughter cells.

Mitosis is divided into a series of phases—prophase, prometaphase, metaphase, anaphase, and telophase—that result in the division of the cell nucleus. Karyokinesis is also called mitosis.

Figure \(\PageIndex{3}\): 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)

Video \(\PageIndex{2}\): Real Microscopic Mitosis (Medical Research Community via www.youtube.com/watch?v=L61Gp_d7evo)

 

Prophase

During prophase, 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.

Prometaphase and Metaphase

During prometaphase, 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. 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 \(\PageIndex{4}\): 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, 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.

Anaphase

During anaphase, 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.

Telophase

During telophase, 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.

 

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

4

Exercise \(\PageIndex{2}\)

Chemotherapy drugs such as vincristine and colchicine disrupt mitosis by binding to the protein tubulin (the subunit of microtubules) and interfering with microtubule assembly and disassembly. Exactly what mitotic structure is targeted by these drugs and what effect would that have on cell division?

Answer

The mitotic spindle is formed of microtubules. Microtubules are polymers of the protein tubulin; therefore, it is the mitotic spindle that is disrupted by these drugs. Without a functional mitotic spindle, the chromosomes will not be sorted or separated during mitosis. The cell will arrest in mitosis and die.

 

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 to separate the two new cells.

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 \(\PageIndex{5}\): 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.

Exercise \(\PageIndex{3}\)

Consider the events of interphase and mitosis. What cell cycle events will be affected in a cell that produces mutated (non-functional) condensin proteins?

Answer

If condensin is not functional, chromosomes are not packaged after DNA replication in the S phase of interphase. It is likely that the proteins of the centromeric region, such as the kinetochore, would not form. Even if the mitotic spindle fibers could attach to the chromatids without packing, the chromosomes would not be sorted or separated during mitosis.

 

 

Contributors and Attributions

• Connie Rye (East Mississippi Community College), Robert Wise (University of Wisconsin, Oshkosh), Vladimir Jurukovski (Suffolk County Community College), Jean DeSaix (University of North Carolina at Chapel Hill), Jung Choi (Georgia Institute of Technology), Yael Avissar (Rhode Island College) among other contributing authors. Original content by OpenStax (CC BY 4.0; Download for free at http://cnx.org/contents/185cbf87-c72...f21b5eabd@9.87).

• Figure \(\PageIndex{1}\):

• John W. Kimball. This content is distributed under a Creative Commons Attribution 3.0 Unported (CC BY 3.0) license and made possible by funding from The Saylor Foundation.

   

 

How to "count" the chromosomes

After DNA replication copies the chromosomes during S phase, sister chromatids remain held together by cohesin proteins. These sisters are still "counted" as one chromosome, until they separate during anaphase of mitosis, which ensures that each of the two new cells inherits one copy (sister chromatid) of each chromosome.

Video \(\PageIndex{3}\) : Following chromosome movements in mitosis

 

 

Example \(\PageIndex{1}\)

If a cell has 10 chromosomes (total), how many chromosomes will be present during metaphase of mitosis? During anaphase? In the two daughter cells?

Solution

10 chromosomes (each made of two sister chromatids because DNA replication occurred in S phase before mitosis) are present during metaphase.

20 chromosomes are present during anaphase because the sister chromatids have been pulled apart.

After telophase and cytokinesis, the new daughter cells will each have 10 chromosomes, which is identical to the parental cell.

Exercise \(\PageIndex{4}\)

Brown bears (Ursus arctos) have 74 (2n=74) chromosomes per diploid cell. How many chromosomes and sister chromatids are present at each of the following stages: G₁, G₂, anaphase of mitosis, and after cytokinesis?

Answer

	# Chromosomes	# Chromatids
G1	74	74
G2	74	148
Anaphase of Mitosis	148	148
Cytokinesis	74	74

 

Exercise \(\PageIndex{5}\)

Human cells have 23 pairs of chromosomes. How many chromosomes are present during metaphase? During anaphase? In the cells that have completed mitosis?

Answer

Metaphase: 46 chromosomes

Anaphase: 92 chromosomes

After mitosis: Each cell has 46 chromosomes.