Information

Is nuclear DNA immuno-privileged?


It is well known that if DNA occurs in the cytoplasm of eukaryotic cells, an immune response may be triggered through a myriad of DNA receptors and pathways as part of the immuno response. Yet, apparently the nuclear DNA does not induce any type of such response. Is it known why this happens? Is it just due to the fact that the nuclear DNA is immuno-privileged?


Pattern recognition receptors (PRRs) can potentially discriminate between endogenous and exogenous DNA:

Microbial nucleic acids can be discriminated from self nucleic acids using various parameters, such as their sequence, their tertiary structure, their molecular modifications and their localization. In addition, mislocalized DNA and RNA can be an indicator of cellular damage and infection. [1]

and

Microbial nucleic acids are discriminated from self nucleic acids based on different parameters, such as their sequence, structure, molecular modifications and localization. On the other hand, mislocalized self nucleic acids - such as extranuclear DNA or extracellular RNA - can be recognized as DAMPs, probably because they are reliable indicators of cellular damage. [2]

Somewhat suspect is the similarity of those quotes; I only link to both reviews so as to include both in the references for further reading.

Distinguishing by sequence and structure are self-explanatory. Molecular modifications could include unmethylated CpG sites which are more common in bacterial and viral genomes and are recognized by TLR9. [3] Mislocalized DNA means any that is found outside the nucleus, which is a sign of damage or infection. Most of the well-studied nucleic-acid-recognizing PRRs are found outside the nucleus: TLRs are constrained to endosomes and the extracellular environment while RLRs are found in the cytoplasm. The as of yet identified DNA sensors like DAI also seem to localize to the cytoplasm. Extranuclear PRRs do not necessarily need to discriminate between endogenous and exogenous DNA: any that they sense is mislocalized. However, at least one dsDNA-recognizing PRR, IFI16, localizes to the nucleus as well as the cytoplasm, where it can recognize viral dsDNA. [4]

It has been assumed that cells distinguish viral from cellular DNA due to the former's presence in the cytosol. However,… Kerur et al. (2011) propose that the DNA genome of Kaposi's sarcoma-associated herpesvirus (KSHV) is recognized inside the nucleus by the DNA sensor IFI16, leading [to] inflammasome activation. [5]

IFI16 apparently distinguishes exogenous from endogenous DNA by its length. [6]

Endogenous DNA is present in vivo as chromatin and the amount of exposed linker DNA between histones is too short to promote the cooperative binding and oligomerization that IFI16 requires for signalling (B). An older model, where IFI16 binds independently, is also shown (A), but it suggests that IFI16 should bind self-DNA and doesn't fit with experimental results.

That is just one specific example of how a PRR can distinguish self from non-self. DNA sensors actually seem to be on the cutting edge of research into the innate immune system and, as such, the complete picture has yet to be determined.


References:

  1. Broz P, Monack DM. 2013. Newly described pattern recognition receptors team up against intracellular pathogens. Nat Rev Immunol 13(8):551-565.
  2. Desmet CJ, Ishii KJ. 2012. Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 12(7):479-491.
  3. Yoneyama M, Fujita T. 2010. Recognition of viral nucleic acids in innate immunity. Rev Med Virol 20(1):4-22.
  4. Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S, Otageri P, Chandran B. 2011. IFI16 Acts as a Nuclear Pathogen Sensor to Induce the Inflammasome in Response to Kaposi Sarcoma-Associated Herpesvirus Infection. Cell Host Microbe 9(5):363-375.
  5. Unterholzner L, Bowie AG. 2011. Innate DNA Sensing Moves to the Nucleus (comment on Kerur et al., 2011). Cell Host Microbe 9(5):351-353.
  6. Morrone SR, Wang T, Constantoulakis LM, Hooy RM, Delannoy MJ, Sohn J. 2014. Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy. PNAS 111(1):62-67.

Long interspersed nuclear element

Long interspersed nuclear elements (LINEs) [1] (also known as long interspersed nucleotide elements [2] or long interspersed elements [3] ) are a group of non-LTR (long terminal repeat) retrotransposons that are widespread in the genome of many eukaryotes. [4] [5] They make up around 21.1% of the human genome. [6] [7] [8] LINEs make up a family of transposons, where each LINE is about 7,000 base pairs long. LINEs are transcribed into mRNA and translated into protein that acts as a reverse transcriptase. The reverse transcriptase makes a DNA copy of the LINE RNA that can be integrated into the genome at a new site.

The only abundant LINE in humans is LINE1. The human genome contains an estimated 100,000 truncated and 4,000 full-length LINE-1 elements. [9] Due to the accumulation of random mutations, the sequence of many LINEs has degenerated to the extent that they are no longer transcribed or translated. Comparisons of LINE DNA sequences can be used to date transposon insertion in the genome.


Chapter 6 Biology

a. TEMs utilize much higher quality glass lenses than those found in light microscopes.

b. Staining with atoms of heavy metal provides higher contrast that the colored dyes used in light microscopy.

c. Specimens visualized by TEM are much thicker than those observed by light microscopy.

a. a using a magnifying glass

b. standard light microscopy

c. scanning electron microscopy

a. a using a magnifying glass

b. standard light microscopy

c. scanning electron microscopy

a. a using a magnifying glass

b. standard light microscopy

c. scanning electron microscopy

a. Prokaryotic cells have cell walls, while eukaryotic cells do not.

b. Eukaryotic cells have flagella, while prokaryotic cells do not.

c. Eukaryotic cells have membrane-bound organelles, while prokaryotic cells do not.

a.the absence of a nucleus

b.the number of mitochondria in the cytoplasm

c. the ratio of surface area to volume of cytoplasm

a. Cut the cube into eight smaller cubes.

b.Flatten the cube into a pancake shape.

c. Round the clay up into a sphere.

a. Cell 1 because it has the smallest volume and will not produce as much waste as the other cells.

b. Cell 2 because it has the highest ratio of surface area to volume, which facilitates the exchange of materials between a cell and its environment.

c. Cell 3 because it has the largest surface area, which will enable it to eliminate its wastes most efficiently.

a. It regulates the movement of proteins and RNAs into and out of the nucleus.

b. It synthesizes the proteins required to copy DNA and make mRNA.

c.It synthesizes secreted proteins.

a. closing of nuclear pores

b. the inability of the nucleus to divide during cell division

c. a loss of genetic information from chromosomes

a. Prokaryotes cannot secrete proteins because they lack an endomembrane system.

b. Proteins secreted by prokaryotes are likely synthesized on ribosomes bound to the cytoplasmic surface of the plasma membrane.

c.The mechanism of protein secretion in prokaryotes is probably the same as that in eukaryotes.

a. producing large quantities of proteins for secretion

b. producing large quantities of proteins in the cytosol

c.producing large quantities of carbohydrates to assemble an extensive cell wall matrix

a. storage of large quantities of water

b.import and export large quantities of protein

c. active secretion of large quantities of protein

a. rough ER → Golgi → transport vesicle → nucleus

b.Golgi → rough ER → lysosome → transport vesicle → plasma membrane

c.rough ER → Golgi → transport vesicle → plasma membrane

a. The mitochondria are most likely defective and do not produce adequate amounts of ATP needed for lipid metabolism.

b. The rough endoplasmic reticulum most likely contains excess ribosomes, which results in overproduction of the enzyme involved in lipid breakdown.

c. The lysosomes most likely lack sufficient amounts of the enzymes necessary for lipid breakdown.

b.only in the nucleus and mitochondria

c. only in the nucleus and chloroplasts

a. with water molecules to generate hydrogen peroxide

b. with oxygen molecules to generate hydrogen peroxide

c. with hydrogen peroxide to generate oxygen

a. endosymbiosis of an oxygen-using bacterium in a larger bacterial host cell-the endosymbiont evolved into chloroplasts

b. endosymbiosis of a photosynthetic archaeal cell in a larger bacterial host cell to escape toxic oxygen-the anaerobic archaea evolved into chloroplasts

c. endosymbiosis of an oxygen-using bacterium in a larger bacterial host cell-the endosymbiont evolved into mitochondria

a. a bacterium, but not a eukaryote

b.an animal, but not a plant

c.nearly any eukaryotic organism

a. membrane proteins of the inner nuclear envelope

b. free ribosomes and ribosomes attached to the ER

c.components of the cytoskeleton

b. eukaryotic flagella and motile cilia

c. eukaryotic flagella, motile cilia, and nonmotile cilia

a. assembly of actin filaments to form bulges in the plasma membrane

b. assembly of microtubule extensions that vesicles can follow in the direction of movement

c. reinforcement of the pseudopod with intermediate filaments

a. conformational changes in ATP that thrust microtubules laterally

b. conformational changes in microfilaments

a. form cleavage furrows during cell division

b. migrate by amoeboid movement

c. separate chromosomes during cell division

b. contraction of muscle fibers

c. extension of pseudopodia

a. The cytoskeleton is a static structure most resembling scaffolding used at construction sites.

b. Although microtubules are common within a cell, actin filaments are rarely found outside of the nucleus.

c. Movement of cilia and flagella is the result of motor proteins causing microtubules to move relative to each other.

a. connecting intermediate filaments to microtubules involved in vesicular transport

b. linking the primary and secondary cell walls in plants

c.transmitting signals from the extracellular matrix to the cytoskeleton

a. It glues adjacent cells together.

b. It prevents dehydration of adjacent cells.

c. It forms connections between the cytoplasm of adjacent cells.

a. They must block water and small molecules to regulate the exchange of matter and energy with their environment.

b. They must provide a rigid structure that maintains an appropriate ratio of cell surface area to volume.

c. They are constructed of materials that are synthesized in the cytoplasm and then transported out of the cell for assembly.

Which of the following statements provides the most plausible explanation for the results of this experiment?

a. The two species of sponge had different enzymes that functioned in the reassembly process.

b. The molecules responsible for cell-cell adhesion (cell junctions) were irreversibly destroyed during the experiment.

c. The molecules responsible for cell-cell adhesion (cell junctions) differed between the two species of sponge.


Chromatin and Chromosomes

To understand chromatin, it is helpful to first consider chromosomes. Chromosomes are structures within the nucleus that are made up of DNA, the hereditary material. In prokaryotes, DNA is organized into a single circular chromosome. In eukaryotes, chromosomes are linear structures. Every eukaryotic species has a specific number of chromosomes in the nuclei of its body’s cells. For example, in humans, the chromosome number is 46, while in fruit flies, it is eight. Chromosomes are only visible and distinguishable from one another when the cell is getting ready to divide. When the cell is in the growth and maintenance phases of its life cycle, proteins are attached to chromosomes, and they resemble an unwound, jumbled bunch of threads. These unwound protein-chromosome complexes are called chromatin (Figure 2) chromatin describes the material that makes up the chromosomes both when condensed and decondensed. We will focus on chromatin and chromosomes in greater detail later.

Figure 2. (a) This image shows various levels of the organization of chromatin (DNA and protein). (b) This image shows paired chromosomes. (credit b: modification of work by NIH scale-bar data from Matt Russell)


Biological Concerns

Mitochondrial transfer and other assisted reproductive technologies have opened the door to a series of biological, ethical, and legal concerns in a world where designer babies could be just around the corner.

The use of mitochondrial transfer is controversial as there are still several safety concerns. For example, there are concerns that some mutant mitochondria may accidentally get carried over from the mother. If this carry-over occurs, many question if the child will develop a mitochondrial disorder later in life or pass on mitochondrial disorders to their offspring. Additionally, there are concerns about the side effects of having DNA from three parents in one person. Research in cell culture or in primates suggests that these issues do not affect the health of the child however everything could change when this technique is used in humans. The scientific community will closely follow any child conceived using mitochondrial transfer to determine if it is safe to continue using.

The medical community is also concerned about the rapid expansion of this technology before these safety concerns have been addressed. This is especially true in places like the Ukraine, where this technology is not regulated this is in contrast to the United States, where it is banned, or the United Kingdom, where it is conditionally allowed only to treat mitochondrial disorders. Dr. Valery Zukin, director of the Nadiya Clinic, leads a Ukrainian team that uses mitochondrial transfer to treat infertility. He has successfully helped at least 4 couples have seemingly healthy children using mitochondrial transfer, as these couples had failed to conceive through conventional in vitro fertilization (IVF). Before the birth of these children, it was unclear if the technique would work for general fertility issues, and it remains unknown what aspect of the treatment helps overcome these issues. Some speculate the donor mitochondria help overcome undiagnosed metabolic problems, but more research must be done before the medical community expands the technique.


Characteristics and Characterization of Human Pluripotent Stem Cells

Anne G. Bang , Melissa K. Carpenter , in Essentials of Stem Cell Biology (Second Edition) , 2009

Somatic Cell Nuclear Transfer

Somatic cell nuclear transfer (SCNT) takes advantage of a unique property of the oocyte cytoplasm that allows somatic nuclei to be reprogrammed to a pluripotent state. In this case, the nucleus of a somatic cell is transferred into an enucleated oocyte. The somatic nucleus is then reprogrammed, and partial development to the ICM stage can occur in culture, followed by either transplantation into a prepared uterus in order to generate cloned animals, or harvesting the ICM to generate ESC lines (reviewed in Yang et al., 2007 Gurdon and Melton, 2008 ). In 2005, a group in South Korea reported the generation of human ESCs from patient specific blastocysts created using SCNT. Unfortunately, this work was later shown to be fraudulent, and to date, the generation of human ESC lines using SCNT has not been reported.


Nuclear Chromatin of DNA: Position, Structure and Functions | Biology

Nuclear chromatin, also called nuclear reticulum, is a darkly stained (Gr. chroma=colour) network of long and fine threads, called chromatin fibres, suspended in most of the nucleoplasm of the interphase nucleus.

It was first reported by W. Flemming (1879).

Structure:

During interphase, nuclear chromatin is in the form of chromatin fibres, each about 100 A in diameter and being formed of a core of DNA and being covered by a proteinous coat.

On the basis of their staining properties with acetocarmine or feulgen (basic fuchsin) and nature of DNA, Chromatin is differentiated into two types (Emile Heitz, 1928):

It is formed of condensed regions (about 250 A in diameter) which are more darkly stained, called heteropycnosis as is with condensed DNA which is transcriptionally inactive (little or no RNA synthesis) and late replicating (replicates after the replication of euchromatin and replicates at the end of S-phase of mitotic cycle). It generally lies near the nuclear lamina. It is mainly formed of highly repeated sequences of DNA. It is less sensitive to mutations and resistant to nuclease digestion.

Heterochromatin is of two types:

(a) Facultative heterochromatin:

It represents the temporarily inactivated chromatin during interphase in some cell types of an organism. The amount of facultative heterochromatin varies widely in different cell types and depends upon the stage of differentiation e.g. less in amount in embryonic or undifferentiated cells while more in amount in highly specialized cells.

It forms about 2.5% of the genome. It represents inactive genes at a particular period whose products are not required at that time. In somatic cells of females of the mammals, one of the 2X-chromosomes is facultatively heterochromatized to form sex chromatin or Barr body (First reported by Barr and Bertram, 1944).

In plants like Melandrium and Rumex, one or both sex chromosomes may undergo partially or completely heterochromatization. Y-chromosome of several Dioecious plants and animals (e.g. Drosophila) is also heterochromatized.

(b) Constitutive heterochromatin:

It represents the permanently inactivated chromatin and is generally found near the centromeric regions, telomeres, in the nucleolar organizer regions and adjacent to the nuclear envelope. It probably increases the centromeric strength and acts as the spacer between the vital genes and acts as full stops of transcription.

Centromeric heterochromatin helps in recognition and association of homologous chromosomes during meiosis. It is with more condensed DNA than euchromatin. During interphase, these regions of constitutive heterochromatin aggregate and form chromocentre.

Recently, it has been reported that heterochromatin contains certain polygenes to transcribe rRNA (in the NOR), 5S RNA and tRNA. Its DNA is formed of repeated polynucleotide sequences (about one hundred to one hundred million times) each being formed of about 300 nucleotides and is called Satellite DNA or repetitive or redundant DNA. The genes in heterochromatic region perhaps become active for a short period.

It is true chromatin of interphase nucleus and is formed of thin (30-80 A in diameter), less darkly stained than heterochromatin. It is with loose DNA which is transcriptionally active and early replicating (during early S-phase). It forms most of the nuclear chromatin. It also differs from heterochromatin in their nucleosomal packing.

The chromatin fibres give beaded appearance due to presence of dense regions of DNA and proteins, called chromomeres. During cell division, these chromatin fibres condense by spiralization and dehydration into a number of rods (Hofmeister, 1848), called chromosomes. Term chromosome was coined by Waldayer (1888).

Functions:

(i) Chromatin fibres contain DNA which acts as genetic material.

(ii) These control the synthesis of structural as well as enzymatic proteins.


What is Nucleolus

Nucleolus is the largest structure in the cell nucleus. The nucleolus is responsible for the production of ribosomes. This process is referred to as the ribosome biogenesis. The nucleolus also has two other roles: assembling the signal recognition particles and generating the cells’ response to stress. The nucleolus is formed around specific chromosomal regions and it is made up of DNA, RNA and associated proteins. The malfunctioning of nucleoli causes illnesses, diseases, disorders and syndromes in humans. The nucleolus can be observed under the electron microscope as a part of the nucleus.

Nucleolus Structure

The nucleolus is composed of three components: the dense fibrillar component (DFC), the fibrillar center (FC) and the granular component (GC). Newly transcribed rRNAs that are bound with the ribosomal proteins are contained in the DFC. GC contains ribosomal proteins bound with RNA. These ribosomal proteins are assembled into immature ribosomes. The nucleolus can be seen only in higher eukaryotes. The evolution of the nucleolus occurred from bipartite organization with the transition of anamniotes to amniotes. The original fibrillar component is separated into FC and DFC due to the substantial increase in the DNA intergenic region. In plant nucleoli, nuclear vacuole can be identified as a clear area at the center of the nucleolus. The nucleolus in the nucleus is shown in figure 1.

Figure 1: Nucleolus in the nucleus

Function of Nucleolus

During the ribosome biogenesis, RNA polymerase I transcribes rRNA genes responsible for 28S, 18S, and 5.8S rRNA transcripts within the nucleus. The 5S rRNA is transcribed by RNA polymerase III. The genes responsible for ribosomal proteins are transcribed by RNA polymerase II. Ribosomal proteins are translated in the cytoplasm during the conventional pathway and imported back into the nucleolus. After the maturation and association of rRNA and ribosomal proteins, they produce 40S and 60S subunits of the 80S ribosome in eukaryotes. Other than ribosomal biogenesis, nucleolus captures proteins and immobilize them in a process known as nucleolar detention.


Nuclear DNA content of some important plant species

Nuclear DNA contents of more than 100 important plant species were measured by flow cytometry of isolated nuclei stained with propidium iodide.Arabidopsis exhibits developmentally regulated multiploidy and has a 2C nuclear DNA content of 0.30 pg (145 Mbp/1C), twice the value usually cited. The 2C value for rice is only about three times that ofArabidopsis. Tomato has a 2C value of about 2.0 pg, larger than commonly cited. This survey identified several horticultural crops in a variety of families with genomes only two or three times as large asArabidopsis these include several fruit trees (a pricot, cherry, mango, orange, papaya, and peach). The small genome sizes of rice and the horticultural plants should facilitate molecular studies of these crops.

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Function of Cell Nucleus

Animal Cell Nucleus

This generic animal cell has all the components that every animal cell has. The cell nucleus can be seen on the left side of the cell. It is the large purple circle. Remember that this is a cross-section view, and in reality the nucleus would be more of a sphere. In animal cells it usually takes a spherical shape if there is enough room within the cell. The nucleus is surrounded by the endoplasmic reticulum, which is covered in spots by ribosomes. When the animal cell divides, the nucleus breaks up, and the nuclear envelope falls apart. The nuclear envelope is then reassembled around each new nucleus after the chromosomes have been divided.

Plant Cell Nucleus

Above is a generic plant cell. Notice how it has a rigid shape, due to the presence of a cell wall. Further, a large central vacuole occupies the majority of the cell, pushing all the other constituents to the sides of the cell. The nucleus here is orange, shown with a chunk taken out to expose the interior. Like animal cell nuclei, this cell nucleus will retain a spherical shape if there is enough room. Oftentimes in plant cells, the central vacuole expands with water to apply pressure to the cell walls. This pressure forces the nucleus into a more flattened, oblong shape. As with animal cell nuclei, this cell nucleus will break down during cell division. Unlike animal cells, plant cells must build new cell walls between dividing cells. The two new nuclei must be moved away from the metaphase plate, or the nuclei may become damaged by the formation of the cell wall.

Other Examples of Cell Nuclei

1. Why is it helpful for a cell to protect its DNA within a cell nucleus?
A. To shield from chemical changes
B. To protect from physical damage
C. Both of the above

2. As mentioned early in this article, mitochondria also contain DNA. Are mitochondria a different form of cell nucleus?
A. Yes, any organelle with DNA is a nucleus.
B. No, their DNA doesn’t produce anything
C. No, because mitochondrial DNA isn’t protected the same way

3. When looking at stained nuclei under a microscope, you notice that some appear uniformly colored, while other appear almost empty, with most of the color clumped together in the middle. What is happening?
A. The cells are dividing
B. Your stain is not working properly
C. The cells are from different species


Watch the video: Spike Protein Goes to Nucleus and Impairs DNA Repair In-Vitro Study (January 2022).