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

Um centrossoma é o principal organizador de microtúbulos de uma célula eucariótica e desempenha um papel vital na formação do fuso mitótico, um arranjo bipolar de microtúbulos que separa as cromátides irmãs. Os dois pólos do fuso são formados por dois centrossomas opostos.
Antes do ciclo celular, no entanto, a maioria das células animais contém apenas um centrossomo no citoplasma. A quinase dependente de ciclina G1 / S ou complexo Cdk - consistindo de ciclina E e Cdk2 em células animais - ajuda a desencadear a duplicação do centrossomo, bem como a entrada no ciclo celular. 
Cada centrossomo consiste em dois centríolos, que são encapsulados por uma matriz pericentriolar proteica.
A duplicação do centrossomo começa no início da fase G1, quando a separase realiza o desengajamento dos dois centríolos. Uma proteína pertencente à família da proteína quinase semelhante ao polo, Plk-4, é um importante regulador para a biogênese do centríolo em humanos.
Perto do início da fase S, um centríolo filho começa a crescer em ângulo reto com a base de cada centríolo.
Durante o G2, os centríolos filhos normalmente terminam de se alongar. Os quatro centríolos permanecem próximos no centrossomo até que a célula entre em mitose.
No início da mitose, o centrossomo se divide em dois, o que também é conhecido como disjunção do centrossomo. Os dois centrossomas resultantes contêm um par de centríolos e a matriz pericentriolar. Ambos os centrossomas nucleam um conjunto de microtúbulos, principalmente no centríolo-mãe, formando coletivamente o fuso mitótico.
O ciclo de vida do centrossoma e do cromossomo é semelhante em vários aspectos. Sua duplicação ocorre apenas uma vez por ciclo e ambas se duplicam por meio de um processo semiconservativo em que uma nova cópia é produzida a partir da cópia pai pré-existente.
Além disso, como os cromossomos, uma cópia do centrossomo é igualmente distribuída para cada célula-filha após a divisão.
A duplicação excessiva do centrossomo pode prejudicar a montagem do fuso mitótico e fazer com que os cromossomos se separem incorretamente, o que pode causar doenças como o câncer.

<ol>
	<li style="margin-left: 0.5in;">Fujita, Hiroki, Yuki Yoshino e Natsuko Chiba. 2015. "Regulação do Ciclo do Centrossomo." Oncologia Molecular e Celular 3 (2). https://doi.org/10.1080/23723556.2015.1075643.</li>
	<li style="margin-left: 0.5in;">Nigg, Erich A. e Andrew J. Holland. 2018. "Uma vez e apenas uma vez: mecanismos de duplicação de centríolos e sua desregulação na doença." Nature Reviews Molecular Cell Biology 19 (5): 297–312. https://doi.org/10.1038/nrm.2017.127.</li>
</ol>

duplicação de centrossoma

Centrosome Duplication

O principal centro organizador de microtúbulos (MTOC) nas células animais é o centrossoma. Um centrossoma possui dois centríolos cilíndricos em seu núcleo. Cada centríolo consiste em nove conjuntos de três microtúbulos unidos por proteínas. Os centríolos são posicionados perpendicularmente entre si e cercados por uma nuvem proteica disforme chamada matriz pericentriolar, ou material pericentriolar (PCM). Para garantir que cada célula filha receba um centrossoma após a divisão celular, a duplicação do centrossoma começa no início do ciclo celular. A duplicação do centrossoma é rigorosamente regulada pelos controles do ciclo celular - como a quinase 2 dependente de ciclina (Cdk2) - para evitar que ocorra mais de uma vez por ciclo celular. Assim, quando a célula atinge a mitose, ela possui dois centrossomas. A duplicação do centrossoma coincide com as fases do ciclo celular. Durante a fase G1 do ciclo celular, os dois centríolos no centrossoma se separam, um processo denominado desorientação do centrossoma. Durante as fases G1 e S, os centrossomas são duplicados. Um novo centríolo, denominado procentríolo, começa a se formar e se alongar na base de cada um dos dois centríolos existentes. Os procentríolos alongam-se através de S e G2 até ficarem tão grandes quanto os centríolos mais antigos. Os quatro centríolos permanecem próximos uns dos outros dentro do PCM aumentado até a célula entrar na mitose. Durante a fase G2, a γ-tubulina e outras proteínas PCM se acumulam no centrossoma, um processo denominado maturação do centrossoma. Durante a transição entre as fases G2 e M, os centrossomas começam a se separar. Os dois centríolos-mãe são desconectados e as proteínas motoras dos microtúbulos separam os dois centrossomas. Erros na regulação do centrossoma podem causar anormalidades no número de cromossomos e centrossomas. Anormalidades e defeitos do centrossoma na progressão do ciclo centrossomo estão implicados em múltiplas doenças, principalmente no câncer. Proteínas supressoras de tumor e oncogenes estão ligadas a alterações prejudiciais nos centrossomas de células tumorais, tornando essas proteínas um alvo de tratamento atraente.

Duplicação de Centrossoma

O principal centro organizador dos microtúbulos (MTOC) nas células animais é o centrossomo. Um centrossomo tem dois centríolos cilíndricos em seu núcleo. Cada...

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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 Biologia Molecular mostra os processos moleculares da célula através de vídeos de animação claros e concisos. Além disso, nos vídeos de Cientistas em ação, a aplicação desses conceitos é demonstrada por meio de experimentos reais em laboratórios modernos.

Centrosome Duplication in the Cell Cycle

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