Name: apc activates chromosome separation
Uploaded: 2023-04-30T10:14:53.000Z
Duration: 50 s
Channel: JoVE

K12 Standards

Next Generation Science Standards

High School

Life Science

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

HS-LS1-4

Anaphase Promoting Complex

Успешное завершение анафазы также зависит от активности убиквитинлигазы, называемой анафазостимулирующим комплексом или циклосомой APC/C.
Во время перехода в анафазу белок Cdc20 связывается с APC/C и активирует его. Активированный APC/C убиквитинирует регуляторные белки, S-циклины и М-циклины, тем самым нацеливаясь на них для протеасомной деградации.
Деградация циклинов подавляет активность большинства Cdk. Отсутствие циклин-зависимой киназной активности позволяет фосфатазам дефосфорилировать большую часть Cdk-субстратов в клетке, что необходимо для завершения анафазы.

<ol>
	<li>Харпер, Д. Уэйд, Джанет Л. Бертон и Марк Дж. Соломон. "Комплекс, способствующий анафазе: это больше не только для митоза." Genes & Development 16, No17 (2002): 2179-2206. <a href="http://genesdev.cshlp.org/content/16/17/2179.full.pdf">http://genesdev.cshlp.org/content/16/17/2179.full.pdf</a></li>
	<li>Торнтон, Брайан Р., Тесси М. Нг, Мэри Э. Матискела, Кристофер В. Кэрролл, Дэвид О. Морган и Дэвид. Точиски. "Архитектурная карта комплекса, способствующего анафазе." Гены и развитие 20, No4 (2006): 449-460. <a href="http://genesdev.cshlp.org/content/20/4/449.full.pdf+html">http://genesdev.cshlp.org/content/20/4/449.full.pdf+html</a></li>
</ol>

Продвигающий комплекс Анафаза

Поэтапное разрушение специфических белков необходимо для развития и завершения клеточного цикла. Такие белки убиквитинируются убиквитинлигазами, а затем разрушаются протеасомой. SCF (Skp1/Cullin/F-box) и комплекс, способствующий анафазе (APC), представляют собой две важные убиквитинлигазы, участвующие в развитии клеточного цикла. В то время как SCF активен на протяжении всего клеточного цикла, APC активируется во время перехода от метафазы к анафазе. Cdc20 или Cdh1 связывается с APC и активирует его, что приводит к образованию комплексов APCCdc20 и APCCdh1 соответственно. Cdc20 и Cdh1 также помогают APC идентифицировать свои субстраты. APCCdc20 играет важную роль в переходе от метафазы к анафазе. Сестринские хроматиды удерживаются вместе когезинами. Когезиновые кольца должны быть разрушены ферментом сепаразой, чтобы сестринские хроматиды могли двигаться к противоположным полюсам во время анафазы. Однако активность сепаразы ингибируется белком секурином. APCCdc20 убиквитинирует секурин, что приводит к его протеасомной деградации. Это приводит к последующей активации сепаразы. APCCdc20 также убиквитинирует митотические циклины, которые, в свою очередь, инактивируют циклин-зависимые киназы или Cdks. Инактивация Cdks и последующее дефосфорилирование Cdk-субстратов необходимы для завершения клеточного деления.

Ступенчатое разрушение специфических белков необходимо для прогрессирования и завершения клеточного цикла. Такие белки убиквитинируются за счет ...

Education

JoVE Core

Molecular Biology

Молекулярная биология

Unit 2

Раздел 2

Cell Division

Деление клетки

KEY TERMS AND CONCEPTS

ОСНОВНЫЕ ТЕРМИНЫ И ПОНЯТИЯ

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 factors form APC Cdc20 and APC Cdh1 complexes, and they also help APC recognize its target proteins.

APC Cdc20 is essential for sister chromatid separation. Sister chromatids are held together by cohesins, which form rings that must be cut so the chromatids can move to opposite poles during anaphase. Separase is the enzyme that breaks the cohesin rings, but securin keeps separase inactive until APC Cdc20 ubiquitinates securin and sends it for proteasomal degradation.

APC Cdc20 also ubiquitinates mitotic cyclins. This lowers cyclin-dependent kinase, or Cdk, activity. The loss of Cdk activity and the later dephosphorylation of Cdk substrates are needed to finish cell division.

APC Activates Chromosome Separation

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 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...

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

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 APC Cdc20 triggers sister chromatid separation by destroying securin and mitotic cyclins, helping cells move from metaphase to anaphase.

APC Activates Chromosome Separation | JoVE K12

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HS-LS1-2

APC Activates Chromosome Separation

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