Eukaryotic Chromosome Structure and Function

In this eukaryotic chromosome structure and function post we have briefly explained about eukaryotic chromosomes, structure, chromatin, components and functions of eukaryotic chromosomes

Eukaryotic Chromosome Structure

DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms carrying the genetic information in genes. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria. DNA is one of the three major macromolecules that are essential for all known forms of life.

DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases).

It is the sequence of these four nucleobases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription. Within cell’s DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes.

Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

Structure of DNA

DNA is a long polymer made from repeating units called nucleotides. As first discovered by James D. Watson and Francis Crick, the structure of DNA of all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34 Angstroms (3.4 nanometers) and a radius of 10 Angstroms (1.0 nanometers).

Sugar-Phosphate

The backbone of the DNA strand is made from alternating phosphate and sugar residues. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings.

These asymmetric bonds mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are called the 5′ (five prime) and 3′ (three prime) ends, with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group.

One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.

Base Pairs of DNA

The four bases found in DNA are adenine (abbreviated A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar/phosphate to form the complete nucleotide, as shown for adenosine monophosphate. The nucleobases are classified into two types: the purines, A and G, being fused five and six membered heterocyclic compounds, and the pyrimidines, the six membered rings C and T.

A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. In addition to RNA and DNA a large number of artificial nucleic acid analogues have also been created to study the proprieties of nucleic acids, or for use in biotechnology.

Grooves

Twin helical strands form the DNA backbone. Another double helix may be found by tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site.

As the strands are not directly opposite each other, the grooves are unequally sized. One groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove.

As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove.

Base pairing

In a DNA double helix, each type of nucleobase on one strand normally interacts with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with a bonding only to T, and C bonding only to G.

This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature.

As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds. DNA with high GC content is more stable than DNA with low GC-content. Long DNA helices with a high GC content have stronger-interacting strands, while short helices with high AT content have weaker interacting strands.

Chromatin

Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene expression and DNA replication.

The primary protein components of chromatin are histones that compact the DNA. Chromatin is only found in eukaryotic cells. Prokaryotic cells have a very different organization of their DNA which is referred to as a genophore (a chromosome without chromatin).

The overall structure depends on the stage of the cell cycle: during interphase the chromatin is structurally loose to allow access to RNA and DNA polymerases that transcribe and replicate the DNA.

DNA coding genes that are actively transcribed (“turned on”) are more loosely packaged and are found associated with RNA polymerases (referred to as euchromatin) while DNA coding inactive genes (“turned off”) are found associated with structural proteins and are more tightly packaged (heterochromatin).

Chromatin organization

DNA wraps around histone proteins forming nucleosomes; the “beads on a string” structure (euchromatin). Multiple histones wrap into a 30 nm fibre consisting of nucleosome arrays in their most compact form (heterochromatin). Higher-level DNA packaging of the 30 nm fibre into the metaphase chromosome (during mitosis and meiosis).

Components in Chromatin

Eukaryotic Chromosomes

Components in chromatin organization

Histones

Histones are the major structural proteins of chromosomes. The DNA molecule is wrapped twice around a Histone Octamer to make a Nucleosome. Six Nucleosomes are assembled into a Solenoid in association with H1 histones. The solenoids are in turn coiled onto a Scaffold, which is further coiled to make the chromosomal matrix.

Histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes.

They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation. Without histones, the unwound DNA in chromosomes would be very long (a length to width ratio of more than 10 million to one in human DNA).

For example, each human cell has about 1.8 meters of DNA, but wound on the histones it has about 90 micrometers (0.09 mm) of chromatin, which, when duplicated and condensed during mitosis, result in about 120 micrometers of chromosomes.

Classes of Histones

Five major families of histones exist: H1/H5, H2A, H2B, H3, and H4. Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1 and H5 are known as the linker histones.

Eukaryotic Chromosomes

Histones

Functions

Compacting DNA

Histones act as spools around which DNA winds. This enables the compaction necessary to fit the large genomes of eukaryotes inside cell nuclei the compacted molecule is 40,000 times shorter than an unpacked molecule.

Chromatin regulation

Histones undergo posttranslational modifications that alter their interaction with DNA and nuclear proteins. The H3 and H4 histones have long tails protruding from the nucleosome, which can be covalently modified at several places.

Modifications of the tail include methylation, acetylation, phosphorylation, ubiquitination, SUMOylation, citrullination, and ADP-ribosylation. The core of the histones H2A, H2B, and H3 can also be modified.

Combinations of modifications are thought to constitute a code, the so-called “histone code”. Histone modifications act in diverse biological processes such as gene regulation, DNA repair, chromosome condensation (mitosis) and spermatogenesis (meiosis).

Chromatin fibre

With addition of H1, the “beads-on-a-string” structure in turn coils into a 30 nm diameter helical structure known as the 30 nm fibre or filament. This level of chromatin structure is thought to be the form of euchromatin, which contains actively transcribed genes.

Electron microscopic studies have demonstrated that the 30 nm fibre is highly dynamic such that it unfolds into a 10 nm fiber (“beads-on-a-string”) structure when transversed by an RNA polymerase engaged in transcription.

DNA packaging

Prokaryotes do not possess nuclei. Instead, their DNA is organized into a structure called the nucleoid. The nucleoid is a distinct structure and occupies a defined region of the bacterial cell.

This structure is, however, dynamic and is maintained and remodelled by the actions of a range of histone-like proteins, which associate with the bacterial chromosome.

Further Readings

Reference