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

Генетический материал, ДНК, в эукариотической клетке существует внутри ядра в виде линейных структур, называемых хромосомами.
Внутри хромосом двухцепочечная ДНК в основном оборачивается вокруг октамерных ядерных белков, называемых гистонами, образуя нуклеосомы. Несколько негистоновых белков также связываются с ДНК, помогая упаковывать ДНК.
Эти нуклеосомы и негистоновые белки образуют спирали, которые в дальнейшем сворачиваются в петли в массив, образуя упакованный хроматин. Степень уплотнения хроматина позволяет чрезвычайно длинной ДНК поместиться внутри ядра. Во время М-фазы хроматин далее скручивается, образуя конденсированные хромосомы.
Дупликация хромосом включает в себя дублирование всей структуры хроматина, поэтому ДНК и связанные с хроматином белки дублируются. Производство гистонов увеличивается для получения дополнительных белков, необходимых для упаковки вновь синтезированной ДНК в хромосомы.
Репликация точной структуры хроматина дублированной хромосомы жизненно важна для регуляции генов. 
Внутри хромосом уровень упаковки хроматина не всегда однороден. Хромосомы содержат участки с плотно упакованным хроматином, называемым гетерохроматином, и участки со слабо упакованным хроматином, называемым эухроматином.
ДНК гетерохроматина недоступна для транскрипционного механизма, и поэтому гены в этих областях не транскрибируются регулярно. Напротив, ДНК внутри эухроматина более доступна, и, таким образом, гены в этих областях могут быть транскрибированы. 
Это структурное и функциональное значение хроматина делает критически важным точное воспроизведение всей структуры хроматина во время дупликации хромосом.

<ol>
	<li>Грот, Аня, Вальтер Роша, Ален Верро и Женевьева Альмузни. "Проблемы хроматина во время репликации и репарации ДНК." Cell 128 (4)2007: 721–33. [<a href="https://www.sciencedirect.com/science/article/pii/S0092867407001298">исходник</a>]</li>
	<li>Маргерон, Рафаэль и Дэнни Рейнберг. "Структура хроматина и наследование эпигенетической информации." Nature Reviews Genetics 11 (4)2010: 285–96. [<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760772/">Исходный код</a>]</li>
</ol>

Дублирование структуры хроматина

Duplication of Chromatin Structure

Процесс дупликации хромосом во время деления клеток требует разрушения всего генома и повторной сборки хроматина. Структура хроматина должна быть точно унаследована, пересобрана и сохранена в дочерних клетках, чтобы обеспечить распространение линии. Основной единицей хроматина является нуклеосома, состоящая из ДНК, обернутой вокруг октамерных белков-гистонов, и коротких участков линкерной ДНК, разделяющих отдельные нуклеосомы. Гистоновые белки внутри нуклеосомы имеют N-концевые концы, выступающие из ядра, обеспечивая места для различных ковалентных модификаций, которые регулируют структуру и функцию хроматина. Во время репликации, когда ДНК раскручивается, родительские нуклеосомы разрушаются и высвобождаются белки-гистоны. По мере прогресса репликации и формирования дочерних цепей родительские гистоны и дополнительные гистоновые белки, синтезированные во время S-фазы, собираются, позволяя образовывать нуклеосомы. Посттрансляционные модификации гистонов и других эпигенетических доменов ДНК также точно воспроизводятся в дочернем геноме. <h4>Структура хроматина влияет на экспрессию генов</h4> Внутри клетки большая часть генома остается недоступной для факторов транскрипции, поскольку регуляторные и кодирующие последовательности ДНК в основном скрыты внутри нуклеосом. Для экспрессии гена необходимо создать доступные участки для связывания транскрипционных факторов, а также модифицировать гистоны, чтобы реорганизовать структуру хроматина и создать среду, благоприятную для транскрипции. Специфические комплексы регуляторных факторов участвуют в открытии локализованных областей хроматина путем смещения или разрушения нуклеосом. Посттрансляционные модификации хвоста гистонов служат для поддержания активного или неактивного состояния транскрипции. Специфические модификации хвоста гистонов могут снизить уровень уплотнения ДНК, способствуя дестабилизации и смещению нуклеосом, обеспечивая доступ к транскрипционному аппарату для влияния на экспрессию генов.

Процесс дупликации хромосом во время деления клетки требует разрушения всего генома и повторной сборки хроматина. Структура хроматина должна быть...

Education

JoVE Core

Molecular Biology

Молекулярная биология

Unit 2

Раздел 2

Cell Division

Деление клетки

KEY TERMS AND CONCEPTS

ОСНОВНЫЕ ТЕРМИНЫ И ПОНЯТИЯ

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

JoVE Core Molecular Biology showcases the molecular processes of the cell through clear and concise animated video lessons. Additionally, in scientist-in-action videos, these concepts' application is demonstrated through real experiments in modern laboratories.

Chromatin Rebuilding During DNA Replication

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