Name: chromatin rebuilding during dna replication
Uploaded: 2021-04-07T12:12:01.000Z
Duration: 2 min 5 s
Channel: JoVE

Il materiale genetico, il DNA, in una cellula eucariotica esiste all'interno del nucleo come strutture lineari chiamate cromosomi.
All'interno dei cromosomi, il DNA a doppio filamento si avvolge principalmente attorno a proteine nucleari ottamerica chiamate istoni per formare nucleosomi. Diverse proteine non istoniche si associano anche al DNA, aiutando nell'impacchettamento del DNA.
Questi nucleosomi e proteine non istoniche si organizzano per formare bobine che si ripiegano ulteriormente in anelli, in un array, formando cromatina impacchettata. L'entità della compattazione della cromatina consente al DNA estremamente lungo di adattarsi all'interno del nucleo. Durante la fase M, la cromatina si avvolge ulteriormente per formare i cromosomi condensati.
La duplicazione cromosomica comporta la duplicazione dell'intera struttura della cromatina, quindi il DNA e le proteine associate alla cromatina sono tutte duplicate. La produzione di istoni è aumentata per generare le proteine aggiuntive necessarie per impacchettare il DNA appena sintetizzato nei cromosomi.
Replicare l'esatta struttura della cromatina del cromosoma duplicato è vitale per la regolazione genica. 
All'interno dei cromosomi, il livello di impacchettamento della cromatina non è sempre uniforme. I cromosomi contengono regioni con cromatina strettamente impacchettata chiamata eterocromatina e regioni con cromatina debolmente impacchettata chiamata eucromatina.
Il DNA dell'eterocromatina è inaccessibile al meccanismo di trascrizione, e quindi i geni in quelle regioni non vengono trascritti regolarmente. Al contrario, il DNA all'interno dell'eucromatina è più accessibile e quindi i geni in queste regioni possono essere trascritti. 
Questo significato strutturale e funzionale della cromatina rende fondamentale che l'intera struttura della cromatina sia riprodotta accuratamente durante la duplicazione cromosomica.

<ol>
	<li>Groth, Anja, Walter Rocha, Alain Verreault e Geneviève Almouzni. "Sfide della cromatina durante la replicazione e la riparazione del DNA." Cell 128 (4)2007: 721–33. [<a href="https://www.sciencedirect.com/science/article/pii/S0092867407001298">Sorgente</a>]</li>
	<li>Margueron, Raphaël e Danny Reinberg. "Struttura della cromatina ed ereditarietà delle informazioni epigenetiche". Nature Reviews Genetics 11 (4) 2010: 285–96. [<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760772/">Fonte</a>]</li>
</ol>

duplicazione della struttura della cromatina

Duplication of Chromatin Structure

Il processo di duplicazione dei cromosomi durante la divisione cellulare richiede la distruzione dell'intero genoma e il riassemblaggio della cromatina. La struttura della cromatina dev’essere accuratamente ereditata, ri-assemblata e mantenuta nelle cellule figlie per garantire la propagazione del lignaggio.

L'unità di base della cromatina è il nucleosoma, costituito da DNA avvolto attorno a proteine istoniche ottamericane e brevi tratti di DNA linker che separano i singoli nucleosomi. Le proteine istoniche all'interno del nucleosoma hanno le loro estremità N-terminali che sporgono dal nucleo, fornendo siti per varie modificazioni covalenti che regolano la struttura e la funzione della cromatina.

Durante la replicazione, quando il DNA si svolge, i nucleosomi parentali vengono distrutti e le proteine istoniche vengono rilasciate. Man mano che la replicazione progredisce e si formano i filamenti figli, gli istoni parentali e le proteine istoniche aggiuntive sintetizzate durante la fase S vengono assemblati, consentendo la formazione di nucleosomi.

Anche le modificazioni post-traduzionali degli istoni e di altri domini epigenetici nel DNA sono riprodotte fedelmente nel genoma figlia.

La struttura della cromatina influenza l'espressione genica

All'interno di una cellula, la maggior parte del genoma rimane inaccessibile ai fattori di trascrizione, poiché le sequenze di DNA regolatrici e codificanti esistono per lo più nascoste all'interno dei nucleosomi. Affinché un gene si esprima, è necessario creare siti accessibili affinché i fattori di trascrizione si leghino e anche modificare gli istoni per riorganizzare la struttura della cromatina e creare un ambiente permissivo per la trascrizione.

Complessi di fattori regolatori specifici sono coinvolti nell'apertura di regioni localizzate della cromatina mediante spostamento o distruzione dei nucleosomi. Le modifiche post-traduzionali della coda dell'istone servono a mantenere uno stato trascrizionale attivo o inattivo. Modifiche specifiche alla coda dell'istone possono facilitare il livello di compattazione del DNA, facilitando la destabilizzazione e lo spostamento dei nucleosomi, fornendo accesso ai macchinari di trascrizione per influenzare l'espressione genica.

Duplicazione della struttura della cromatina

Il processo di duplicazione cromosomica durante la divisione cellulare richiede la distruzione dell'intero genoma e il riassemblaggio della cromatina. La struttura della cromatina deve essere ...

Education

Didattica

JoVE Core

Molecular Biology

Biologia Molecolare

Unit 2

Unità 2

Cell Division

Divisione cellulare

KEY TERMS AND CONCEPTS

TERMINI E CONCETTI CHIAVE

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 have N-terminal tails that stick out from the core. These tails can receive covalent modifications that help control chromatin structure and function.

As DNA unwinds during replication, parental nucleosomes are disrupted and histone proteins are released. When daughter DNA strands form, the old histones and the extra histone proteins made during S phase are put back together on the DNA. This assembly recreates nucleosomes on the new strands. The same histone marks and other epigenetic features in the DNA are also copied into the daughter genome.

Chromatin structure also affects gene expression. In most cells, much of the genome is not available to transcription factors because regulatory and coding DNA is hidden inside nucleosomes. To turn a gene on, the cell must open a local DNA region so transcription factors can bind. It must also modify histones to rearrange chromatin into a state that supports transcription.

Regulatory factor complexes help open these local chromatin regions by displacing or disrupting nucleosomes. Histone tail modifications can help keep chromatin in an active or inactive state. Some modifications reduce DNA compaction and make nucleosomes easier to destabilize or move. This gives the transcription machinery access to the DNA and helps control gene expression.

Chromatin Rebuilding During DNA Replication

chromatin-rebuilding-during-dna-replication

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 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

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

Explore how chromatin is broken apart and rebuilt during DNA replication, how histones are reused, and how chromatin changes affect gene expression in cells.

Chromatin Rebuilding During DNA Replication | JoVE K12

molecular biology

Le video animazioni di JoVE Core Molecular Biology, organizzate in video lezioni, illustrano i processi molecolari cellulari in maniera chiara e concisa. Inoltre, nei video di "scienziati in azione", i concetti scientifici vengono applicati e dimostrati da ricercatori attraverso esperimenti in laboratorio.

Chromatin Rebuilding During DNA Replication

Description

Transcript

Tags