Name: centrosome duplication in the cell cycle
Uploaded: 2021-04-07T12:12:01.000Z
Duration: 2 min 25 s
Channel: JoVE

Ein Zentrosom ist der Hauptorganisator der Mikrotubuli einer eukaryotischen Zelle und spielt eine wichtige Rolle bei der Bildung der mitotischen Spindel, einer bipolaren Anordnung von Mikrotubuli, die die Schwesterchromatiden trennt. Die beiden Spindelpole werden durch zwei gegeneinander angeordnete Zentrosomen gebildet.
Vor dem Zellzyklus enthalten die meisten tierischen Zellen jedoch nur ein Zentrosom im Zytoplasma. Die G1/S-Cyclin-abhängige Kinase oder Cdk-Komplex, die in tierischen Zellen aus Cyclin E und Cdk2 besteht, trägt dazu bei, die Zentrosomduplikation sowie den Eintritt in den Zellzyklus auszulösen. 
Jedes Zentrosom besteht aus zwei Zentriolen, die von einer proteinhaltigen perizentriolären Matrix verkapselt sind.
Die Zentrosomduplikation beginnt in der frühen G1-Phase, wenn die Separase die Entkopplung der beiden Zentriolen durchführt. Plk-4, ein Protein aus der Familie der Polo-ähnlichen Proteinkinasen, ist ein wichtiger Regulator für die Zentriol-Biogenese beim Menschen.
Zu Beginn der S-Phase beginnt ein Tochterzentrriol im rechten Winkel zur Basis jeder Zentriole zu wachsen.
Während G2 beenden die Töchterzentriolen typischerweise die Verlängerung. Die vier Zentriolen bleiben im Zentrosom dicht beieinander, bis die Zelle in die Mitose eintritt.
Zu Beginn der Mitose teilt sich das Zentrosom in zwei Teile, was auch als Zentrosomdisjunktion bekannt ist. Die beiden resultierenden Zentrosomen enthalten jeweils ein Paar Zentriolen und die perizentrioläre Matrix. Beide Zentrosomen keimen einen Satz von Mikrotubuli, hauptsächlich an der Mutterzentriole, und bilden zusammen die mitotische Spindel.
Der Lebenszyklus von Zentrosom und Chromosom ist in mehreren Aspekten ähnlich. Ihre Duplizierung erfolgt nur einmal pro Zyklus und beide duplizieren sich durch einen semikonservativen Prozess, bei dem eine neue Kopie aus der bereits vorhandenen übergeordneten Kopie erstellt wird.
Wie bei den Chromosomen wird auch eine Kopie des Zentrosoms nach der Teilung gleichmäßig auf jede Tochterzelle verteilt.
Eine übermäßige Zentrosomduplikation kann die mitotische Spindelassemblierung beeinträchtigen und dazu führen, dass sich die Chromosomen nicht richtig trennen, was zu Krankheiten wie Krebs führen kann.

<ol>
	<li style="margin-left: 0.5in;">Fujita, Hiroki, Yuki Yoshino und Natsuko Chiba. 2015. "Regulation des Zentrosomenzyklus." Molekulare und zelluläre Onkologie 3 (2). https://doi.org/10.1080/23723556.2015.1075643.</li>
	<li style="margin-left: 0.5in;">Nigg, Erich A. und Andrew J. Holland. 2018. "Einmal und nur einmal: Mechanismen der Zentriol-Duplikation und ihre Deregulierung bei Krankheiten." Nature Reviews Molecular Cell Biology 19 (5): 297–312. https://doi.org/10.1038/nrm.2017.127.</li>
</ol>

zentrosomenverdopplung

Centrosome Duplication

Das primäre mikrotubuläre Organisationszentrum (MTOC) in tierischen Zellen ist das Zentrosom. Ein Zentrosom besteht im Kern aus zwei zylindrischen Zentriolen. Jede Zentriole besteht aus neun Sätzen von drei Mikrotubuli, die durch Proteine zusammengehalten werden. Die Zentriolen sind rechtwinklig zueinander positioniert und von einer formlosen Proteinwolke umgeben, die als perizentrioläre Matrix oder perizentrioläres Material (PCM) bezeichnet wird.

Um sicherzustellen, dass jede Tochterzelle nach der Zellteilung ein Zentrosom erhält, beginnt die Verdopplung des Zentrosoms früh im Zellzyklus. Die Verdopplung des Zentrosoms wird streng durch Zellzykluskontrollen - wie die zyklinabhängige Kinase 2 (Cdk2)- reguliert, um zu verhindern, dass sie mehr als einmal pro Zellzyklus stattfindet. Wenn die Zelle die Mitose erreicht, hat sie daher zwei Zentrosomen.

Die Verdopplung des Zentrosoms fällt mit den Phasen des Zellzyklus zusammen. Während der G1-Phase des Zellzyklus trennen sich die beiden Zentriolen im Zentrosom, ein Prozess, der als Zentrosom-Desorientierung bezeichnet wird.

Während der G1- und S-Phasen werden die Zentrosomen verdoppelt. Ein neues Zentriol, das als Prozentiol bezeichnet wird, beginnt sich an der Basis jedes der beiden vorhandenen Zentriolen zu bilden und zu verlängern. Die Prozentiolen verlängern sich während der S- und G2-Phasen, bis sie so groß wie die älteren Zentriolen sind. Die vier Zentriolen bleiben innerhalb der vergrößerten PCM bis zum Eintritt der Zelle in die Mitose eng zusammen.

Während der G2-Phase reichern sich γ-Tubulin und andere PCM-Proteine im Zentrosom an, ein Prozess, der als Zentrosomenreifung bezeichnet wird.

Während des Übergangs von der G2- zur M-Phase beginnen sich die Zentrosomen zu trennen. Die beiden Mutterzentriolen werden getrennt, und mikrotubuläre Motorproteine bewegen die beiden Zentrosomen auseinander.

Fehler in der Regulation der Zentrosomen können zu Anomalien in der Anzahl der Chromosomen und Zentrosomen führen. Zentrosomenanomalien und Defekte in der Progression des Zentrosomenzyklus sind in mehreren Krankheiten, insbesondere in Krebs, impliziert. Tumorsuppressorproteine und Onkogene sind mit nachteiligen Veränderungen in den Zentrosomen von Tumorzellen verknüpft, was diese Proteine zu einem attraktiven Behandlungsziel macht.

Zentrosomenverdopplung

Das primäre Mikrotubuli-Organisationszentrum (MTOC) in tierischen Zellen ist das Zentrosom. Ein Zentrosom hat in seinem Kern zwei zylindrische Zentriolen. Jeder...

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centrosome duplication in the cell cycle

Centrosome duplication is a key part of the animal cell cycle. The centrosome is the main microtubule organizing center, or MTOC, in animal cells. It contains two cylindrical centrioles at its core. Each centriole has nine sets of three microtubules held together by proteins. The two centrioles sit at right angles and are surrounded by the pericentriolar matrix, or PCM, a shapeless protein cloud.

Duplication starts early in the cell cycle so each daughter cell can receive a centrosome after cell division. Cell cycle controls keep this process tightly regulated. Cyclin-dependent kinase 2, or Cdk2, helps prevent duplication from happening more than once in a single cell cycle. By the time the cell reaches mitosis, it has two centrosomes.

Centrosome duplication matches the stages of the cell cycle. In G1, the two centrioles separate. This separation is called centrosome disorientation. During G1 and S, new centrioles called procentrioles begin to form at the base of each older centriole. The procentrioles then elongate through S and G2 until they are the same size as the older centrioles.

The four centrioles stay close together inside the enlarged PCM until mitosis begins. During G2, gamma-tubulin and other PCM proteins build up in the centrosome. This step is called centrosome maturation. Between G2 and M, the centrosomes start to separate. The two mother centrioles disconnect, and microtubule motor proteins move the centrosomes apart.

Problems in centrosome regulation can lead to abnormal numbers of centrosomes and chromosomes. These defects are linked to several diseases, especially cancer. Tumor suppressor proteins and oncogenes are associated with harmful changes in tumor cell centrosomes. Because of this, they are important targets for treatment research.

Centrosome Duplication in the Cell Cycle

mitosis and cytokinesis

Mitosis and Cytokinesis Stages

Mitosis and cytokinesis are the two main steps of cell division. Mitosis is the process that divides the nucleus, while cytokinesis splits the rest of the cell. During mitosis, the cell’s genetic material is separated into two sets. This helps form two new nuclei with the same genetic information. Cytokinesis then completes division by separating the cytoplasm, which creates two daughter cells. These stages work together to make cell division possible in growing and repairing tissues.

duplication of chromatin structure

Chromatin Rebuilding During DNA Replication

Chromatin rebuilding during DNA replication helps cells copy DNA and pass on chromosome structure to daughter cells. During cell division, the genome must be disrupted and then reassembled across the whole chromosome. This process allows chromatin to be inherited, rebuilt, and maintained in new cells. The basic unit of chromatin is the nucleosome. A nucleosome contains DNA wrapped around an octamer of histone proteins, with short linker DNA between neighboring nucleosomes. The histone proteins...

cohesins

Cohesins in Meiosis and Genetic Disorders

Cohesin protein complexes act like molecular glue that keeps sister chromatids together. They are important in both mitosis and meiosis. In mitosis, cohesin complexes are removed from chromosomes before anaphase begins. Meiosis has two rounds of chromosome separation. Meiosis I separates homologous chromosomes, while Meiosis II separates sister chromatids. This process produces four daughter cells. The Meiosis I cohesin complex is made of four subunits: Smc1, Smc3, Rec8, and Scc3. Rec8...

condensins

How Condensins Shape Mitotic Chromosomes

Condensins shape chromosomes during mitosis, the stage when a cell divides. These large protein complexes use ATP, the cell’s energy molecule, to help turn loose post-interphase DNA into compact, separate chromosomes. They organize and segregate chromosomal DNA so it can be passed on correctly. Plant and animal cells contain two condensin complexes: condensin I and condensin II. Each complex has five subunits. Two are SMC, or Structural Maintenance of Chromosomes, subunits. One is a kleisin...

the mitotic spindle

How the Mitotic Spindle Separates Chromosomes

The mitotic spindle is a microtubule-based structure that helps separate chromosomes during cell division. It forms in eukaryotic cells and moves sister chromatids to opposite ends of the parent cell. This leaves each new cell nucleus with the correct genetic material. A bipolar spindle has two poles, and that shape is important for chromosome segregation. In many animal cells, two centrosomes are present when mitosis begins. Each centrosome helps organize a circular set of microtubules at one...

centrosome duplication

Centrosome duplication is a key part of the animal cell cycle. The centrosome is the main microtubule organizing center, or MTOC, in animal cells. It contains two cylindrical centrioles at its core. Each centriole has nine sets of three microtubules held together by proteins. The two centrioles sit at right angles and are surrounded by the pericentriolar matrix, or PCM, a shapeless protein cloud. Duplication starts early in the cell cycle so each daughter cell can receive a centrosome after...

microtubule instability

Microtubule Growth and Shrinkage

Microtubules are hollow, cylindrical filaments in the cell. They are about 25 nm wide and can range from 200 nm to 25 μm in length. Their main building blocks are GTP-bound tubulin subunits that form αβ-heterodimers, which then assemble into protofilaments. These protofilaments join by lateral bonds to create stable microtubule cylinders. Microtubules are highly dynamic because they repeatedly assemble and break down. They can even grow on one end while shrinking on the other at the same time.

spindle assembly

How the Mitotic Spindle Forms

The mitotic spindle forms through centrosome-mediated, chromatin-mediated, and microtubule-mediated pathways. These pathways often work at the same time. Together, they build a strong spindle apparatus for cell division. In most cells, centrosomes are the main sites where microtubules begin to grow. During the G2 to prophase transition, centrosomes mature and make more microtubules. The growing microtubules extend from both centrosomes, and their plus-ends search for chromosomes by attaching...

attachment of sister chromatids

Kinetochore-Microtubule Binding in Mitosis

Kinetochore-microtubule binding helps chromosomes line up and separate during mitosis. After the nuclear envelope breaks down, condensed chromosomes are exposed to the bipolar microtubules of the mitotic spindle. The kinetochore is a large, disc-shaped protein complex at the centromere region of each sister chromatid, and it serves as the microtubule binding site. Usually, the plus-end of a single microtubule inserts into the kinetochore. In some cases, a kinetochore first makes lateral...

forces acting on chromosomes

Chromosome Movement During Mitosis

Chromosome movement during mitosis depends on several small forces that act at different times and positions in the cell. In prometaphase, these forces help chromosomes move to the equatorial plane and line up at the metaphase plate. Because the forces change with location and stage, chromosome behavior also changes as mitosis continues. Microtubules and motor proteins create two main kinds of force on chromosomes: poleward force and anti-poleward force, also called polar-ejection force.

separation of sister chromatids

Anaphase Start and Chromatid Release

Anaphase starts when sister chromatids are released from one another and pulled toward opposite spindle poles. Before that happens, cohesion along the chromosomal arms is reduced from prophase to metaphase, which helps the sister chromatids resolve. A residual cohesin link still holds them together until the metaphase-to-anaphase transition. This leftover connection helps prevent early separation and reduces the risk of aneuploidy, or the wrong number of chromosomes, in daughter cells. At the...

the spindle assembly checkpoint

How Cells Safeguard Chromosome Separation

The spindle assembly checkpoint helps cells safeguard chromosome separation during anaphase. It acts as a molecular surveillance system. The checkpoint checks whether the steps needed for chromosome segregation are complete before the cell moves on. Many proteins work together to control this checkpoint. If mutations affect these proteins, a cell may enter anaphase too early. Chromosomes can then separate before the needed steps are finished. When this happens, the daughter cells may receive...

anaphase a and b

Chromatid Movement by Microtubule Forces

Chromatid movement during anaphase depends on microtubule forces at the spindle. Kinetochore microtubules grow from the spindle poles, and their plus ends attach to kinetochores on sister chromatids. The kinetochore protein complex Ndc80 makes low-affinity links with the microtubule plus end.

the contractile ring

How Cells Build the Contractile Ring

Contractile rings are built from microfilaments and help separate daughter cells during cytokinesis. This ring forms as the cell cycle moves forward, but the exact timing and coordination with other cell cycle events are still not fully understood. RhoA, a small GTPase in the Ras superfamily, controls contractile ring assembly and function. The inactive form of RhoA is bound to GDP. A guanine nucleotide exchange factor, or Rho-GEF, is located in the cortex region, where the next cell division...

determining the plane of cell division

How Cells Set the Division Plane

How cells set the division plane during cell division affects daughter cell size and, in many cases, cell fate. The plane of division is perpendicular to the plane of chromosome segregation. Different organisms use different cues to place it, based on their shape and needs. In animal cells, the cleavage furrow forms along the division plane from the cell cortex, the area just below the plasma membrane. The mitotic spindle is the main guide for this position. If the spindle axis changes, the...

the phragmoplast

How Plant Cells Build a New Wall

Plant cells build a new wall during cytokinesis with help from the phragmoplast. This plant structure forms from the central spindle and related cell parts as the cell finishes dividing. In animal cells, the comparable structure is the midbody, but in plants the phragmoplast expands outward to guide new wall formation. The mature phragmoplast has a donut-like shape. It has an outer leading region, a middle transition zone, and an inner lagging region. New microtubules are assembled...

distribution of cytoplasmic content

How Organelles Are Split During Cytokinesis

Cytokinesis splits a cell’s chromosomes and organelles into two daughter cells. Before cell division, organelles grow and divide. They cannot be made from scratch, so each daughter cell must inherit at least one copy to survive. Many details of this organelle sorting process are still not fully known. The cytoplasm contains organelles, salts, proteins, and water. Small organelles such as peroxisomes and lysosomes can be shared by simple diffusion. Because cells contain many copies of these...

anaphase promoting complex

APC Activates Chromosome Separation

The anaphase-promoting complex, or APC, helps control cell cycle progression by destroying specific proteins at the right time. These proteins are tagged with ubiquitin by ubiquitin ligases and then broken down by the proteasome. The SCF (Skp1/Cullin/F-box) complex and APC are two major ubiquitin ligases involved in this process. SCF stays active throughout the cell cycle, but APC turns on during the metaphase-to-anaphase transition. APC becomes active when Cdc20 or Cdh1 binds to it. These...

key terms and concepts

Learn how centrosomes duplicate during G1, S, G2, and M phases, how Cdk2 regulates the process, and why centrosome errors are linked to cancer.

Centrosome Duplication in the Cell Cycle | JoVE K12

molecular biology

JoVE Core Molecular Biology veranschaulicht die molekularen Prozesse der Zelle in prägnanten animierten Video-Lektionen. In Videos von Wissenschaftlern in Aktion wird die Anwendung dieser Konzepte zusätzlich durch reale Experimente in modernen Laboren demonstriert.

Centrosome Duplication in the Cell Cycle

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