Name: cohesins in meiosis and genetic disorders
Uploaded: 2021-04-07T12:12:01.000Z
Duration: 2 min 20 s
Channel: JoVE

During S-phase of the cell cycle in eukaryotes, chromosomal duplication produces two identical copies of each chromosome called sister chromatids.
The sister chromatids formed are held together by a set of protein complexes called cohesins. The cohesin rings exist as clamps around the sister chromatids at multiple locations along their length, preventing them from drifting apart.
Cohesin complexes contain four subunits: Smc1, Smc3, Scc1, and Scc3. The Smc1 and Smc3 are coiled-coil proteins with a hinge domain at one end and an ATPase head domain at the other end. The hinge domains of Smc1 and Smc3 bind directly to each other, while an Scc1 subunit connected to an Scc3 subunit bridges the head domains of Smc1 and Smc3, forming a ring-like structure.
The hinge domain of the cohesin ring-structure can be triggered to open and close, facilitating cohesin loading on the chromosomes.
As cells progress through mitotic prophase, sister chromatid resolution takes place, involving dissociation of cohesin rings along the chromosomal arms while preserving those bound to the centromere region. The differential removal of cohesins causes the sister chromatids to become partially separated along

cohesins

Cohesins

Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
<h4>Cohesin complexes in Meiotic Division</h4>
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions&#8212; Meiosis I followed by Meiosis II &#8211; producing four daughter cells. Meiosis I includes the separation of homologous chromosomes, whereas Meiosis-II involves the separation of sister chromatids.
The Meiosis I cohesin complex consists of four subunits &#8211; Smc1, Smc3, Rec8 (replacing Scc1 from mitotic cohesin complex), and Scc3 &#8211; forming a ring-like structure.
During Meiosis I, entire chromosomes segregate towards the opposite poles as cohesin removal takes place only from the chromosomal arms. Cohesin is still maintained at the centromere region, allowing the sister chromatids to remain connected. During the metaphase I to anaphase I transition, the differential cohesin removal is facilitated by the separase-mediated cleavage of the Rec8 subunit of cohesins along the chromosomal arms. The centromeric Rec8 is protected from cleavage by association with a protector protein Shugoshin (Sgo1).
<h4>Cohesinopathies</h4>
Cohesins contribute to the maintenance of genomic stability. Mutations in genes coding for cohesin subunits or cohesin co-factors can lead to diseases called cohesinopathies. Cornelia de Lange syndrome (CdLS) and Roberts syndrome are two best-described cohesinopathies. CdLS is a neurodevelopmental disorder causing mental retardation, facial dysmorphism, upper limb abnormalities, and growth delay. Roberts syndrome results in craniofacial abnormalities, limb reduction, and growth retardation in affected patients.

Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In ...

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JoVE Core

Molecular Biology

Unit 2

Cell Division

KEY TERMS AND CONCEPTS

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 replaces Scc1, which is found in the mitotic cohesin complex. These subunits form a ring-like structure. During Meiosis I, cohesin is removed from the chromosome arms, but it remains at the centromere. The centromere is the region that keeps sister chromatids connected. This allows whole chromosomes to move toward opposite poles during the metaphase I to anaphase I transition.

Cohesin removal on the arms happens when separase cleaves the Rec8 subunit. Centromeric Rec8 is protected from cleavage by Shugoshin, also called Sgo1. Cohesins also help maintain genomic stability. Changes in genes for cohesin subunits or cohesin co-factors can cause cohesinopathies. Two well-known examples are Cornelia de Lange syndrome, which can cause neurodevelopmental problems, facial differences, upper limb abnormalities, and slow growth, and Roberts syndrome, which can cause craniofacial abnormalities, limb reduction, and growth retardation.

Cohesins in Meiosis and Genetic Disorders

cohesins-in-meiosis-and-genetic-disorders

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...

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

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 cohesins act in mitosis and meiosis, how Rec8 and Shugoshin control chromosome separation, and how cohesin mutations can cause disease.

Cohesins in Meiosis and Genetic Disorders | JoVE K12

molecular biology

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Cohesins in Meiosis and Genetic Disorders

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