The genetic information of an organism is stored in the form of nucleic acids. Nucleic acids, DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are long linear polymers composed of nucleotide building blocks. Each nucleotide is comprised of a sugar, a phosphate residue, and a nitrogenous bases (a purine or pyrimidine). DNA is longer than RNA and contains the entire genetic information of an organism encoded in the sequences of the bases. In contrast, RNA only contains a portion of the information and can have completely different functions in the cell.
DNA is structurally characterized by its double helix: two opposite, complementary, nucleic acids strands that spiral around one another. The DNA backbone, with alternatively linked sugar and phosphate residues, is located on the outside. The bases are located inside the helix and form the base pairs adenine and thymine or guanine and cytosine, which are linked by hydrogen bonds.
The human genome comprises 3.2 x 109 base pairs, which are distributed over 23 pairs of chromosomes. Each chromosome is a linear DNA molecule of a certain length. The chromosome is only well visualized under the light microscope during the metaphase of mitosis, as it is maximally condensed during this phase. Chromosomes are present as pairs in most cells of the body. One chromosome in each of the 23 pairs originates from the mother and the other from the father.
Both interrelated chromosomes are termed homologous because they each have a variant of the same gene. Alterations in the number or structure of the chromosomes lead to various conditions, e.g., developmental disorders. Chromosomal assessment with different molecular biology and cytogenetic methods often allows for a clear diagnosis.
NucleoSides consist of base and Sugar (deoxyribose). NucleoTides consist of base, deoxyribose and phosphaTe.
- Cytosine has 3 H-bond donors and forms a strong bond with guanine, which has 3 H-bond acceptors.
- Other than uracil, there are many other bases that may be created after the initial nucleic acid chain formation, for example:
- Amino acids required for purine synthesis
- See “ ” for more details.
|Overview of pyrimidines and purines|
|Rings||Base||Notable characteristics||As a nucleoside unit in RNA||As a nucleoside unit in DNA|
|Pyrimidines|| || || || || |
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|Purines|| || || || |
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“A mean person GAGs a PURring cat!” (Three Amino acids, Glycine, Aspartate, and Glutamine, are necessary for PURine synthesis.)
“C-G stabilizes DNA Crazy Good!” (C-G bonds are extremely stable.)
“PYRates Capture 1 Undersea Treasure.” (PYRimidine bases: Cytosine, Thymine, and Uracil and consist of 1 ring.)
“PURe A Glass for 2.” (PURine bases are Adenine and Guanine and consist of 2 rings.)
Nucleic acid sugars
- Structure: The sugar found in nucleic acids is a pentose, which has a five-atom ring.
- Bases via N-glycosidic bonds
- Phosphate residue via phosphodiester bonds
- A nucleotide can have one, two, or three phosphate groups (also termed “nucleoside monophosphate”, “diphosphate”, and “triphosphate”, respectively).
- Nucleic acids are composed of nucleoside monophosphates.
Nucleoside diphosphates and nucleoside triphosphates (e.g., ATP) are found in biochemical processes requiring energy
- The phosphoanhydride bonds store a high amount of energy that can be utilized in biochemical processes when targeted by 3' hydroxyl attack.
- The nucleotide that is added to the 5' end of the nucleic acid initially has three phosphate groups. The splitting of the two end phosphate groups supplies the energy necessary for the phosphodiester bonds that build the DNA backbone.
Function of nucleotides and their derivates
- Building blocks of nucleic acids
- Source of energy: : especially as a universal energy carrier of the cell in the form of ATP, but also GTP
- Signal molecules: especially the second messenger cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate) , both phosphoric esters
Activators for the transfer of groups: Through the potential of forming energy-rich bonds, nucleotides are able to transfer a molecule onto another in biosynthesis, e.g.:
- UDP-Glucose is an active form of glucose in glycogenesis.
- Dietary choline can be activated to citicoline by CTP and be used in the synthesis of phosphatidylcholine.
- 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) serves as a sulfate group donor in sulfatide synthesis.
- S-Adenosyl methionine (SAM) is formed from methionine and serves as a cofactor in methylation reactions.
- Regulators: enzyme reactions in signal transduction pathways (e.g., activates GTP G proteins)
- Carrier molecules: e.g., the electron carrier nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) as a component of coenzymes in redox reactions
The energy carrier ATP contains ribose and not deoxyribose as a sugar, and therefore has a 2' OH group.
Overview of nucleic acids
- Long, linear chains (polymers) of nucleotides
- Alternating sugar and phosphate residues of individual nucleotides, linked by phosphodiester bonds, form the backbone
- Primary structure of nucleic acids: nucleotide sequence in the chain
- Phosphodiester bonds are negatively charged.
- The chemical composition of nucleic acids (DNA and RNA) and their structure of repetitive nucleotide units allow them to function as both information carrier and mediator.
|DNA vs. RNA|
|Sugar|| || |
|Length|| || |
|Function|| || |
Overview of double-stranded DNA
Organization of the human genome
- Double-stranded chain of deoxyribonucleotides in cells
- Both strands are complementary to each other and run anti-parallel.
- Nucleotides form single-stranded DNA that stabilizes into double-stranded DNA
- DNA conforms into right-handed double helix that binds histone octamers to form nucleosomes (appear as “beads on a string” under electron microscopy)
- Chromatin formation begins, which is then further compacted
- During replication (mitosis or meiosis), chromatin maximally condenses into chromosomes (only visible during metaphase under light microscopy)
- 3D structure of DNA in which two polynucleotide strands are intertwined, stabilized by:
- Specific base pairing via hydrogen bonds (H bonds) between complementary nucleobases of DNA
- Hydrophobic effect: The negatively charged sugar-phosphate backbone is located on the outside of the helix, the bases on the inside.
- Base stacking: The base pairs are stacked on one another (stacking interactions) and interact through van der Waals forces, which have an additional stabilizing effect.
- Double helix has a minor groove and a major groove.
- B conformation (B-DNA)
- A conformation (A-DNA)
- Z conformation (Z-DNA)
- Description: winded double helix , also termed “superhelix”
- Occurrence: especially in circular DNA molecules
- Function: Supercoiled DNA molecules have a more compact structure than the relaxed form of DNA.
- In palindromic sequences, a sequence of base pairs occurring over a certain segment is read identically on both complementary DNA strands, i.e., the sequence always reads the same on both strands in a 5'→3' direction.
- Bases may be present between the palindromic sequences that are not complementary.
- These segments are self-complementary and can form a hairpin loop.
- Results in the formation of a cross-shaped structure in double-stranded DNA
- Function: Some proteins that are capable of binding DNA require palindromic sequences as a recognition sequence, e.g., steroid hormone receptors or restriction enzymes.
- Definition: complex of DNA and its associated proteins (both histones and non-histones) structured as repetitive units (nucleosomes)
- Condensation and organization of DNA (a very large molecule) allow for storage inside the nucleus and are important for gene regulation
- Opening chromatin structure from a compact state to a more accessible arrangement
- Allows for transcription factors and RNA polymerase to access specific loci of genes
- Facilitated by various enzyme remodelers (e.g., SWI/SNF ATPases), histone post-translational modifications (see below), and direct modification of DNA itself (e.g., DNA demethylation).
Heterochromatin is Hooked tight while Euchromatin is Easygoing.
- Definition: group of proteins that bind to DNA in the nucleus of eukaryotes to support the structure of chromatin
Types: There are four core histones and a linker.
4 Core histones: H2A, H2B, H3, H4
- 2 molecules of each core histone form the nucleosome 8-protein complex core, a histone octamer, around which the DNA is wound in segments
Controls gene expression via reversible post-translational modification of histones (acetylation, methylation, phosphorylation, ubiquitinylation, Sumoylation, ADP-ribosylation)
- Histone methylation
- Acetylation of specific lysine residues (positively charged) in histone proteins → less positively charged histones → weaker binding of DNA → relaxation of DNA coiling → ↑ transcription activity
- Similarly, histone deacetylation via histone deacetylase tightens the coiling of DNA and decreases transcription activity (see “”).
- Clinical implications: pathogenesis of Huntington disease (dysregulated acetylation); thyroid hormone-induced acetylation that influences thyroid hormone synthesis
- Linker histone (H1)
- 4 Core histones: H2A, H2B, H3, H4
Nucleosome (nucleosome core particle)
- Definition: a structural and functional complex of DNA (∼ 150 bp) and histone octamer that gives chromatin its “beads on a string” appearance
- 30 nm chromatin fiber (solenoid)
- Chromatin loop
See “” for more information.
- A denser packaging of chromatin that only becomes visible under the microscope during cell division (especially in metaphase)
- Number of chromosomes in the human genome:
- Structure: A chromosome pair consists of 2 identical chromatids connected at the center by a centromere.
- The human genome consists of ∼ 3.2 billion base pairs (bp).
- The DNA stored in a human cell would total ∼ 1.8 m in length.
- In addition to the nuclear genome (found in the nucleus), there is also a mitochondrial genome that largely codes for RNA-associated proteins
- ∼ 10% contains genes and related sequences
∼ 90% does not contain genes
- The function of ∼ 50% of DNA sequences is unknown.
∼ 45% is composed of repetitive sequences (repetitive genetic elements).
- Simple repetitive DNA elements (tandem repeats)
- Previously mobile genetic elements (such as , LTR , non-LTR, LINE , SINE )
- ∼ 24% of the genome is spanned by introns.
Mitochondrial genome (mitochondrial DNA, mtDNA)
RNA: Structure and characteristics
RNA classes and their structure
RNAs can be differentiated into various types, which differ in their length, structure, and function. Depending on the type, RNA can be a single-stranded or double-stranded segment.
|Classification of RNA|
|mRNA (messenger RNA)|| |
|tRNA (transfer RNA)|| |
|rRNA (ribosomal RNA)|
|snRNA (small nuclear RNA)|| |
|snoRNA (small nucleolar RNA)|| |
| RNA component of signal recognition particles |
(scRNA; small cytoplasmic RNA)
|Telomerase RNA component (human telomerase RNA, hTR)|
|miRNA (microRNA)|| |
|siRNA (small interfering RNA)|
“CCA Can Catch Amino acids” (function of the 5'-CCA-3' sequence in tRNA).