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

생명의 근본적인 부분은 세포가 게놈을 복제하고 분열하는 능력이며, 이러한 과정은 세포 주기의 두 가지 주요 단계에 걸쳐 발생합니다.
첫째, S기에서는 염색체 DNA가 복제됩니다. M기 동안, 복제된 염색체는 분리되어 유전적으로 동일한 두 개의 딸세포로 분포합니다.
S기 이후, 자매 염색체의 DNA는 매우 길고 얽혀 있습니다. 이 상태에서 자매 염색분체를 분리하면 염색체 파괴, 부적절한 분리, 심지어 세포 사멸로 이어질 수 있습니다.
이러한 잠재적인 위기를 피하기 위해 세포는 초기 유사분열 동안 상당한 양의 에너지를 쏟아 자매 염색분체를 더 쉽게 분리되는 더 짧은 구조로 점차적으로 재조직합니다.
이 재편성은 염색체의 응축에 관여하는 단백질 복합체인 콘덴신(condensin)에 의존합니다.
콘덴신은 5개의 서브유닛으로 구성됩니다. 진핵생물에서 두 개의 주요 소단위인 SMC2와 SMC4는 다른 세 개의 소단위(1개의 kleisin과 2개의 HEAT-repeat 소단위)에 의해 ATPase 헤드 도메인에서 연결되어 있습니다.
응축물은 ATP 가수분해에 의해 생성된 에너지를 사용하여 자매 염색체 분리를 촉진하는 두 가지 주요 과정, 즉 염색체 응축과 자매 염색체 해상도를 촉진합니다.
염색체가 응축되는 동안 염색체는 단단히 채워집니다. 자매 염색분체(sister chromatid) 해상도 동안, 응집체(cohesin)의 부분적 제거에 의해 자매 DNA가 분리되거나 분리될 때 응축된 자매 염색분체는 별개의 구조가 됩니다.
세포가 중기에 도달할 때쯤이면 자매 염색분체는 팔을 따라 느슨하게 연결되어 있지만 중심체에서는 여전히 단단히 연결되어 있습니다. 
콘덴신은 DNA 코일링을 변경하고 DNA 루프를 둘러싸는 고리 구조를 형성하여 염색체 응축 및 자매 염색체 해상도를 촉매할 수 있습니다.

<ol>
	<li>배티, 폴, 다니엘 W. 게를리치. 2019. "유사분열 염색체 역학: 세포가 게놈을 분리하는 방법." 세포 생물학 동향 29 (9): 717–26. https://doi.org/10.1016/j.tcb.2019.05.007. </li>
	<li>스키벤스, 로버트 V. 2019. "응축과 코헤신 – 이 중 하나는 다른 것과 같지 않습니다!" 세포 과학 저널, 132 (3). https://doi.org/10.1242/jcs.220491. </li>
</ol>

콘덴신

Condensins

콘덴신은 유사분열 동안 염색체 조립에 연료를 공급하기 위해 ATP를 사용하는 큰 단백질 복합체입니다. 이는 염색체 DNA를 압축하고, 조직하고, 분리함으로써 뒤엉키고 형태가 없는 덩어리의 간기 이후 DNA를 개별화된 염색체로 변환합니다.

식물과 동물 세포에는 두 가지 유형의 콘덴신 복합체인 콘덴신 I과 콘덴신 II가 포함되어 있습니다. 두 복합체 모두 5개의 하위 단위, 즉 2개의 SMC(염색체 구조 유지) 하위 단위, 1개의 클라이신 하위 단위, 2개의 HEAT 반복 하위 단위로 구성되어 있습니다.

콘덴신 I과 콘덴신 II의 핵심 하위 단위는 SMC2와 SMC4입니다. SMC 단백질은 ATP 의존적 방식으로 DNA 배열을 변경합니다. 나머지 3개의 하위 단위(비SMC 또는 보조 하위 단위)는 두 복합체 간에 다릅니다.

척추동물 콘덴신이 고갈된 연구에서는 유사분열 염색체 형성에서 콘덴신 I과 II의 뚜렷한 역할이 밝혀졌습니다. 콘덴신 II 제거는 염색체를 더 길고 유연하게 만들고, 염색체 얽힘, 후기 동안의 부피가 큰 염색질 연결 및 전기의 급격한 단축을 초래합니다. 대조적으로, 콘덴신 I을 제거하면 염색체가 더 짧고 넓어지며 후기의 붕괴가 발생하여 덜 심각하지만 여전히 세포질 분열 실패를 초래합니다.

콘덴신이 염색체를 압축하는 방법에 대한 대중적인 설명은 루프 압출 모델입니다. 이 모델은 콘덴신 분자가 근처의 두 DNA 부위에 결합하여 반대 방향으로 미끄러져 성장하는 DNA 루프를 생성할 수 있다고 가정합니다. 응축물은 또한 서로 상호작용하여 염색질의 먼 부분을 연결하는 다량체를 형성할 수도 있습니다.

콘덴신 돌연변이는 여러 유형의 암과 연관되어 있습니다. 예를 들어, 콘덴신 II 하위단위 유전자에 과오 돌연변이가 있는 쥐에서는 T 세포 림프종이 발생했습니다. 콘덴신이 염색체 구조에 영향을 미치는 메커니즘은 아직 밝혀지고 있지만, 이러한 단백질 복합체는 세포 주기와 세포 생존에 필수적입니다.

콘덴신은 유사분열 동안 염색체 조립에 연료를 공급하기 위해 ATP를 사용하는 큰 단백질 복합체입니다. 그들은 얽히고 형체없는 덩어리를 변형시킵니다 ...

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 2

제2단원

Cell Division

세포 분열

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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

JoVE Core 분자생물학은 명확하고 간결한 애니메이션을 통해 분자 단계에서 일어나는 세포 과정을 설명합니다.또한, 과학자가 직접 실험을 진행하는 실사 영상을 통해 분자생물학 개념의 응용 사례를 보여줍니다.

How Condensins Shape Mitotic Chromosomes

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