Name: how condensins shape mitotic chromosomes
Uploaded: 2021-04-07T12:12:01.000Z
Duration: 2 min 15 s
Channel: JoVE

Fundamentalną częścią życia jest zdolność komórki do replikacji swojego genomu i podziału; procesy te zachodzą w dwóch głównych fazach cyklu komórkowego.
Po pierwsze, w fazie S chromosomalne DNA ulega duplikacji. Podczas fazy M zduplikowane chromosomy są rozdzielane i dystrybuowane do dwóch genetycznie identycznych komórek potomnych.
Po fazie S DNA chromatyd siostrzanych jest bardzo długie i splątane. Oddzielenie chromatyd siostrzanych w tym stanie może prowadzić do pęknięć chromosomów, nieprawidłowej segregacji, a nawet śmierci komórki.
Aby zapobiec temu potencjalnemu kryzysowi, komórka poświęca znaczną ilość energii podczas wczesnej mitozy na stopniową reorganizację siostrzanych chromatyd w krótsze struktury, które łatwiej się rozdzielają.
Ta reorganizacja opiera się na kondensinie, kompleksie białkowym biorącym udział w kondensacji chromosomów.
Kondensacja składa się z pięciu podjednostek. U eukariontów dwie główne podjednostki, SMC2 i SMC4, są połączone w swoich domenach głównych ATPazy przez trzy pozostałe podjednostki: jedną podjednostkę kleizyny i dwie podjednostki powtórzeń HEAT.
Kondensyny wykorzystują energię generowaną przez hydrolizę ATP do promowania dwóch głównych procesów, które ułatwiają separację chromatyd siostrzanych: kondensacji chromosomów i rozdzielczości chromatyd siostrzanych.
Podczas kondensacji chromosomów chromatydy stają się ciasno upakowane. Podczas rozdzielczości chromatyd siostrzanych, skondensowane chromatydy siostrzane stają się odrębnymi strukturami, gdy siostrzane DNA są rozłączane lub dekatenowane przez częściowe usunięcie kohezyn.
Zanim komórka osiągnie metafazę, chromatydy siostrzane są tylko luźno połączone wzdłuż ramion, ale nadal są ściśle połączone w centromerach. 
Kondensyna może zmieniać zwijanie DNA i katalizować kondensację chromosomów oraz rozdzielczość chromatyd siostrzanych poprzez tworzenie pierścieniowych struktur, które otaczają pętle DNA.

<ol>
	<li>Batty, Paul i Daniel W. Gerlichowie. 2019. "Mechanika chromosomów mitotycznych: jak komórki segregują swój genom." Trendy w biologii komórki 29 (9): 717–26. https://doi.org/10.1016/j.tcb.2019.05.007. </li>
	<li>Skibbens, Robert V. 2019. "Kondensyny i kohezyny – jedna z tych rzeczy nie jest taka sama jak druga!" Dziennik Nauki o Komórkach 132 (3). https://doi.org/10.1242/jcs.220491. </li>
</ol>

kondensyny

Condensins

Kondensyny to duże kompleksy białkowe, które wykorzystują ATP do napędzania składania chromosomów podczas mitozy. Przekształcają splątaną, bezkształtną masę pointerfazowego DNA w zindywidualizowane chromosomy poprzez zagęszczanie, organizowanie i segregację chromosomalnego DNA. Komórki roślinne i zwierzęce zawierają dwa rodzaje kompleksów kondensynowych – kondensynę I i kondensynę II. Obydwa kompleksy mają pięć podjednostek: dwie podjednostki SMC (Structural Maintenance of Chromosomy), podjednostkę Kleisina i dwie podjednostki HEAT-repeat. Podstawowymi podjednostkami zarówno kondensyny I, jak i kondensyny II są SMC2 i SMC4. Białka SMC zmieniają układ DNA w sposób zależny od ATP. Pozostałe trzy podjednostki - podjednostki inne niż SMC lub pomocnicze - różnią się między tymi dwoma kompleksami. Badania, w których wyczerpano się kondensyny kręgowców, wykazały odrębną rolę kondensyn I i II w tworzeniu chromosomów mitotycznych. Usunięcie kondensyny II skutkuje dłuższymi, bardziej elastycznymi chromosomami, splątaniem chromosomów, nieporęcznymi mostkami chromatyny podczas anafazy i drastycznym skróceniem profazy. Natomiast usunięcie kondensyny I prowadzi do krótszych, szerszych chromosomów i zakłócenia anafazy, które jest mniej poważne, ale nadal skutkuje niepowodzeniem cytokinezy. Popularnym wyjaśnieniem sposobu, w jaki kondensyny zagęszczają chromosomy, jest model wytłaczania pętlowego. Model ten zakłada, że cząsteczka kondensyny może wiązać się z dwoma pobliskimi miejscami DNA i przesuwać je w przeciwnych kierunkach, tworząc rosnącą pętlę DNA. Kondensyny mogą również oddziaływać ze sobą, tworząc multimery łączące odległe segmenty chromatyny. Mutacje kondensyny powiązano z kilkoma typami nowotworów. Na przykład u myszy z mutacją zmiany sensu w genie podjednostki kondensyny II rozwinął się chłoniak z komórek T. Chociaż mechanizmy, poprzez które kondensyny wpływają na architekturę chromosomów, są wciąż wyjaśniane, te kompleksy białkowe są integralną częścią cyklu komórkowego i przeżycia komórek.

Kondensyny

Kondensyny to duże kompleksy białkowe, które wykorzystują ATP do napędzania składania chromosomów podczas mitozy. Przekształcają splątaną, bezkształtną masę ...

Education

JoVE Core

Molecular Biology

Biologia molekularna

Unit 2

Jednostka 2

Cell Division

Podział komórki

KEY TERMS AND CONCEPTS

Kluczowe terminy i pojęcia

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 subunit, and two are HEAT-repeat subunits. The core SMC subunits in both complexes are SMC2 and SMC4, which change DNA arrangement in an ATP-dependent way. The other three subunits are non-SMC, or auxiliary, subunits, and they differ between condensin I and condensin II.

Studies in vertebrate cells show that condensin I and condensin II have distinct roles in mitotic chromosome formation. When condensin II is removed, chromosomes become longer and more flexible. They can also become tangled, form bulky chromatin bridges during anaphase, and move into a much shorter prophase. When condensin I is removed, chromosomes become shorter and wider. The anaphase defect is less severe, but cytokinesis still fails.

One common explanation for chromosome compaction is the loop extrusion model. In this model, a condensin molecule binds two nearby DNA sites and slides them in opposite directions. This creates a growing DNA loop. Condensins may also work together as multimers that connect distant parts of chromatin. Condensin mutations have been linked to several cancers, including T cell lymphomas in mice with a missense mutation in a condensin II subunit gene. Researchers are still working out exactly how condensins control chromosome structure, but these protein complexes are important for the cell cycle and cell survival.

How Condensins Shape Mitotic Chromosomes

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

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

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 condensins compact and organize DNA during mitosis, how condensin I and II differ, and why these protein complexes matter for cell division and cancer.

How Condensins Shape Mitotic Chromosomes | JoVE K12

molecular biology

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How Condensins Shape Mitotic Chromosomes

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