DNA

DNA is two-stranded and forms a double helix. Each nucleotide consists of a nitrogenous base, a deoxyribose sugar, and a phosphate group. Hydrogen bonds can form between nitrogenous bases, which include purines and pyrimidines:

  • Adenine - purine

  • Thymine - pyrimidine

  • Guanine - purine

  • Cytosine - pyrimidine

One turn of a double helix measures 3.32 nm. The two strands of DNA are antiparallel. The following points describe the structural aspects of DNA:

  • The ring of pi electrons between stacked purines and pyrimidines is nonpolar, minimizing interaction with water.

  • Hydrogen bonds maintain the correct orientation of strands.

  • Stacking of planar bases stabilizes the molecule due to the cumulative effect of van der Waals forces.

  • Water also stabilizes DNA.

  • DNA's overall negative charge requires shielding from water and cations to minimize destabilizing forces between negative charges.

Mutations

  • Point Mutation: Identity of a single base changes.

  • Transition Mutation: A pyrimidine is substituted for another pyrimidine, or a purine for another purine.

  • Transversion Mutation: A pyrimidine is swapped for a purine or vice versa.

  • Single-Nucleotide Polymorphism (SNP): A variation at a single position in DNA among individuals, affecting traits and susceptibility to diseases.

  • Silent Mutation: No discernible effect on function.

  • Missense Mutation: Observable effect on function.

  • Nonsense Mutation: A change that results in a premature stop codon, yielding an incomplete and usually nonfunctional protein.

  • Indel: Insertion or deletion of a base in a DNA sequence.

  • Frameshift Mutation: An indel that is not divisible by three, resulting in an altered or truncated polypeptide.

DNA can be damaged by low levels of ionizing radiation. Tautomeric shifts can lead to base mispairing during DNA replication. Thousands of purines are lost daily from DNA in human cells. If the repair mechanism fails to replace them, a point mutation occurs. Additionally, bases may spontaneously deaminate.

A-DNA:

  • Partially dehydrated DNA.

  • Base pairs are tilted 20 degrees from the horizontal.

  • Distance between base pairs and turns is reduced.

  • Diameter increases.

Z-DNA:

  • Slimmer and left-handed.

  • Alternating pyrimidine and purine bases are more likely to adopt this conformation.

  • 4.56 nm turn distance with a zigzag formation.

DNA Supercoiling:
A critical aspect of DNA structure that facilitates compact storage and regulates gene expression by influencing DNA accessibility to various proteins.

  • Underwound: Fewer than the normal number of turns, leading to higher negative supercoiling, enhancing transcription and replication processes.

  • Overwound: More than the standard number of turns, resulting in positive supercoiling that hinders unwinding necessary for transcription and replication.

In prokaryotic cells, a chromosome is typically circular, allowing efficient packaging of genetic material. A nucleoid is an irregularly shaped region where chromosomal DNA is located, crucial for regulating gene expression. Nucleoid-associated proteins are small, positively charged proteins that assist in the organization and stabilization of DNA.

In eukaryotes, DNA molecules are singular and linear, complexed with histone proteins called chromatin, which package DNA into a compact form for efficient gene regulation and protection during cell division.

Histones:

  • Small basic proteins that bind to DNA and form nucleosomes, consisting mainly of lysine and arginine.

  • Histone Fold: A structural motif that includes three alpha helices and two loops, facilitating binding to DNA.

Histone Modifications:
Covalent modifications of histone tail residues, known as histone modifications, can regulate gene expression, influence chromatin structure, and affect DNA accessibility. These include acetylation, methylation, phosphorylation, and ubiquitination, referred to as epigenetic modifications.

Chromatin:
A complex of DNA and proteins that serves as the structural basis of chromosomes in eukaryotic cells, allowing for compact storage and regulatory control of genetic information.