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

生命の基本的な部分は、細胞がゲノムを複製して分裂する能力であり、これらのプロセスは細胞周期の2つの主要な段階で発生します。
まず、S期には染色体DNAが複製されます。M期では、複製された染色体が分離され、遺伝的に同一の2つの娘細胞に分配されます。
S期に続いて、姉妹染色分体のDNAは非常に長く、もつれています。この状態で姉妹染色分体を分離すると、染色体の切断、不適切な分離、さらには細胞死につながる可能性があります。
この潜在的な危機を回避するために、細胞は初期の有糸分裂中にかなりの量のエネルギーを、姉妹染色分体をより簡単に分離する短い構造に徐々に再編成するために費やします。
この再編成は、染色体の凝縮に関与するタンパク質複合体であるコンデンシンに依存しています。
コンデンシンは5つのサブユニットで構成されています。真核生物では、SMC2とSMC4という2つの主要なサブユニットは、他の3つのサブユニット(1つはクライシン、2つはHEATリピートサブユニット)によってATPaseヘッドドメインで接続されています。
コンデンシンは、ATP加水分解によって生成されたエネルギーを使用して、シスター染色分体の分離を促進する2つの主要なプロセス、すなわち染色体凝縮とシスター染色分体分離を促進します。
染色体凝縮中、染色分体は密集します。姉妹染色分体分解中、凝縮した姉妹染色分体は、コヒーシンの部分的な除去によって姉妹DNAが結合解除または脱分離されると、明確な構造になります。
細胞が中期に達するまでに、姉妹染色分体は腕に沿って緩く接続されているだけですが、セントロメアではまだしっかりとつながっています。 
コンデンシンは、DNAのコイルを変化させ、DNAのループを取り囲む環状構造を形成することにより、染色体の凝縮と姉妹染色分体分離を触媒することができます。

<ol>
	<li>バッティ、ポール、ダニエル・W・ガーリッヒ。2019.「有糸分裂染色体力学:細胞がゲノムを分離する方法」 細胞生物学の動向 29(9):717–26。https://doi.org/10.1016/j.tcb.2019.05.007。 </li>
	<li>Skibbens, Robert V. 2019. 「凝縮物とコヒーシン – これらのものの一つは他のものとは違う!」 Journal of Cell Science 132 (3). https://doi.org/10.1242/jcs.220491. </li>
</ol>

コンデンシン

Condensins

コンデンシンは、ATPを使用して有糸分裂中の染色体の集合を促進する大きなタンパク質複合体です。彼らは、染色体DNAを圧縮、組織化、分離することによって、間期後DNAのもつれ合った形のない塊を個別の染色体に変換します。

植物細胞と動物細胞には、コンデンシンIとコンデンシンIIという2種類のコンデンシン複合体が含まれています。両方の複合体には5つのサブユニットがあります:2つのSMC(染色体の構造維持)サブユニット、クライシンサブユニット、および2つのHEAT-repeatサブユニットです。

コンデンシンIとコンデンシンIIの両方のコア サブユニットはSMC2とSMC4です。SMCタンパク質は、ATP依存的にDNAの配置を変更します。他の3つのサブユニット—非SMCサブユニットまたは補助サブユニット— は、2つの複合体間で異なります。

脊椎動物のコンデンシンが枯渇する研究では、有糸分裂染色体形成におけるコンデンシンIとIIの異なる役割が示されています。コンデンシンIIを除去すると、染色体がより長く、より柔軟になり、染色体のもつれが生じ、後期に大きなクロマチンの架橋が生じ、前期が大幅に短縮されます。 対照的に、コンデンシン I を除去すると、染色体がより短く、より幅広くなり、後期の破壊はそれほど深刻ではありませんが、依然として細胞質分裂不全を引き起こします。

コンデンシンがどのように染色体を圧縮するかについての一般的な説明は、ループ押し出しモデルです。このモデルは、コンデンシン分子が近くの2つのDNA部位に結合し、それらを反対方向にスライドさせて、成長するDNAループを作成できると仮定しています。コンデンシンは互いに相互作用して、クロマチンの離れたセグメントを連結する多量体を形成することもあります。

コンデンシンの変異は、いくつかの種類の癌と関連していると考えられています。たとえば、コンデンシンIIサブユニットの遺伝子にミスセンス変異があるマウスは、T細胞リンパ腫を発症しました。コンデンシンが染色体構造に影響を与えるメカニズムはまだ解明されていませんが、これらのタンパク質複合体は細胞周期と細胞の生存に不可欠です。

コンデンシンは、ATPを使用して有糸分裂中の染色体の集合を促進する大きなタンパク質複合体です。彼らは絡み合った形のない塊を変身させます...

Education

JoVE Core

Molecular Biology

分子生物学

Unit 2

ユニット2

Cell Division

細胞分裂

KEY TERMS AND CONCEPTS

主要用語と概念

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 分子生物学は、明確で簡潔なアニメーション ビデオ レッスンを通じて細胞の分子プロセスを紹介します。さらに、科学者の実際のビデオでは、これらの概念の応用が現代の研究室での実際の実験を通じて実証されています。

How Condensins Shape Mitotic Chromosomes

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