Genetics, Mitosis


Article Author:
Ibraheem Rehman
Hajira Basit
Ahmad Malik


Article Editor:
Brittany Simpson


Editors In Chief:
Sherri Murrell


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
5/10/2019 7:42:35 PM

Introduction

The ability to reproduce is one trait that sets living organisms apart from nonliving matter. The flow of life is based on cell division or the reproduction of cells. Cell division can play a different role in different organisms. For example, when a prokaryotic cell divides, it has completely reproduced because it gives rise to a new organism. However, in multicellular eukaryotes, mitotic cell division is mostly used for growth and replacement or repair of injured cells. Most cell division results in genetically identical daughter cells. This means that a cell cannot divide itself into 2 cells by pinching its cell membrane in half, randomly allocating half of its contents to one cell and half of its contents to another cell. First, a dividing cell replicates its DNA then sends it to opposite sides of the cell. Finally, the cell will divide. This process of replicating DNA and eventually forming 2 identical daughter cells is termed mitosis.[1][2][3]

Cellular

The entirety of a cell’s DNA is called its genome. During cell division, the whole genome is replicated exactly and distributed to 2 daughter cells. A human cell typically has about 2 meters of DNA. Due to the enormous length, the DNA must be highly condensed to fit into the nucleus of each cell. The highly condensed packages of DNA are termed chromosomes when the cell has completed the synthesis phase and is ready to undergo mitosis. Various proteins aid the DNA in folding compactly into subunits of nucleosomes and chromatin. Human somatic cells have 2 sets of 23 chromosomes for a total of 46 chromosomes - 22 sets of autosomes and 1 set of sex chromosomes. Each set of chromsomes is inherited from each parent.[4][5][6] DNA packaging is discussed in a different StatPearls reviews - Genetics, DNA Packaging and Genetics, Histone Code.

Mechanism

The mitotic phase is usually the shortest part of any cell cycle. The largest portion of the cell cycle, interphase, makes up 90% of a cell's life cycle, and is the stage for growing and performing the cellular functions specific to that cell. The interphase is further divided into the G phase and S phase. During these phases, the cell grows by producing various proteins and cytoplasmic organelles. During the S phase, the cell copies all of its chromosomes in preparation for cell division or mitosis. Some cells divide very rarely in their lifetime and are in the G phase. Nerve cells, for example, divide rarely thus remain in the G phase.[7]

Phases

After interphase, mitosis is conventionally divided into 5 phases, which include prophase, prometaphase, metaphase, anaphase and telophase and cytokinesis. In interphase, a nuclear envelope surrounds the nucleus, the DNA is replicated in the S phase, and the sister chromatids join together at the central portion of the chromosome - the centromere. To organize the chromsome motion in the cell to help make division efficient as well as ensure all material is present in both daughter cells, the cell has centrosomes at each pole of the cell. Centrosomes organize the fibers of the mitotic spindle during mitosis that will help pull the sister chromatids apart.

In prophase, the chromatin fibers condense into chromosomes that are visible through a light microscope, each replicated chromosome appears as two identical sister chromatids joined at their centromeres, and the mitotic spindle begins to form. Also, the centrosomes begin to move to opposite poles of the cell, and they are propelled by the lengthening microtubules between them.

In prometaphase, the nuclear envelope falls apart; microtubules can now invade the nuclear area and bind to some of the chromosomes. The microtubules bind at the kinetochores, specialized protein structures at the centromere. Not all microtubules interact with kinetochores. Some microtubules interact with microtubules extending from the other side of the cell.

In metaphase, the centrosomes have migrated to opposite poles of the cell. The chromosomes have all lined up at the metaphase plate in the middle of the cell, and all chromosomes are attached to microtubules through their kinetochores. The metaphase plate is an imaginary line equidistant from the spindle’s 2 poles.

In anaphase, the shortest stage of mitosis, the sister chromatids break apart, and the chromosomes begin moving to opposite ends of the cell. By the end of anaphase, the 2 halves of the cell have an equivalent collection of chromosomes.

In telophase, 2 daughter nuclei form. The nuclear envelope beings to reappear. DNA begins to de-condense while spindle microtubules begin to depolymerize. Mitosis, the division of one nucleus into 2, is now complete. Lastly, cytokinesis, which is the division of the cytoplasm, takes place and the cell divides into 2 separate cells. In animal cells, this is accomplished through a cleavage furrow that pinches the cell in 2.

Clinical Significance

Throughout mitosis, certain checkpoints are essential to the continuation of the process. If certain conditions are not met, mitosis halts. If any of these checkpoints are bypassed without being complete, certain pathology, such as cancer, can occur.[8][9]

There are three main checkpoints in mitosis, and those include the G, G, and M checkpoints. During the G checkpoint, the cell determines that conditions are adequate to divide. In extremely harsh conditions, the cell will not proceed to the S phase. The second checkpoint G is when the cell ensures that all chromosomes have been replicated and that no DNA is damaged. If these conditions are met, then mitosis can begin. Lastly, during metaphase of mitosis, there is another checkpoint that ensures that microtubules have bound all chromosomes' kinetochores. If this is not the case, the sister chromatids do not separate. Only when all sister chromatids have been bound will mitosis proceed into anaphase.

Cancer cells can bypass these checkpoints and divide indefinitely. They do not stop growing even when all growth factors have been depleted. The abnormal behavior of cells can have harmful effects on the body. It starts with a single cell in a specific tissue transforming from a normal cell to a cancer cell. Normally, the body can identify a cancer cell by the proteins on its surface and destroy it. However, if a cancer cell evades destruction, it can form a mass of cancerous cells called a tumor. If the tumor stays in the same place, it is called a benign tumor and can usually be removed with surgery. However, a malignant tumor is one that can spread to other tissues of the body and impair functions of more than one organ. An individual with a malignant tumor is said to have cancer. The spread of cancer cells from one location to another is called metastasis.

Individuals can have a somatic or inherited mutation in certain tumor suppressor genes that will increase their risk of developing cancers. These "tumor suppressor genes" are very often cell cycle regulators that will act as a stop sign to halt cell division in the case of DNA damage, etc. A well-known tumor suppressor, Rb, is associated with development of retinoblastoma.[10]

A localized tumor can be treated with high-energy radiation, which damages DNA in cancer cells much more than DNA in normal cells. This is because cancer cells have the lost the ability to repair DNA. In order to treat metastatic tumors, chemotherapy is used. Chemotherapy is when drugs that are toxic to dividing cells are administered through the circulatory system. One example is the drug Taxol, which freezes the mitotic spindle by preventing microtubule depolymerization, which eventually leads to cell destruction.

Mitosis is a process constantly occurring in the human body. It is important to understand the process at the molecular level because many conditions, such as cancer, can arise when mitosis is interfered with in any way.


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Genetics, Mitosis - Questions

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Before mitosis can be optically observed, the process of ______ has occurred:



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In which phase of mitosis does the genetic material in the cell replicate?



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During which phase of mitosis, does cohesin break apart?



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Genetics, Mitosis - References

References

Miles DM,Desdouets C,Géli V, Histone stress: an unexplored source of chromosomal instability in cancer? Current genetics. 2019 Apr 11;     [PubMed]
Tolić IM,Novak M,Pavin N, Helical Twist and Rotational Forces in the Mitotic Spindle. Biomolecules. 2019 Apr 1;     [PubMed]
Al Jord A,Spassky N,Meunier A, Motile ciliogenesis and the mitotic prism. Biology of the cell. 2019 Mar 24;     [PubMed]
Dou Z,Prifti DK,Gui P,Liu X,Elowe S,Yao X, Recent Progress on the Localization of the Spindle Assembly Checkpoint Machinery to Kinetochores. Cells. 2019 Mar 23;     [PubMed]
Slade D, Mitotic functions of poly(ADP-ribose) polymerases. Biochemical pharmacology. 2019 Mar 22;     [PubMed]
Pradillo M,Evans D,Graumann K, The nuclear envelope in higher plant mitosis and meiosis. Nucleus (Austin, Tex.). 2019 Dec;     [PubMed]
Kaul R,Risinger AL,Mooberry SL, Microtubule-Targeting Drugs: More than Antimitotics. Journal of natural products. 2019 Mar 22;     [PubMed]
Xie M,Bu Y, SKA2/FAM33A: A novel gene implicated in cell cycle, tumorigenesis, and psychiatric disorders. Genes     [PubMed]
Raspelli E,Fraschini R, Spindle pole power in health and disease. Current genetics. 2019 Feb 20;     [PubMed]
Lee WH,Bookstein R,Hong F,Young LJ,Shew JY,Lee EY, Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science (New York, N.Y.). 1987 Mar 13     [PubMed]

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