DNA, the blueprint of life, is a complex molecule with a fascinating structure. Its shape, formed by complementary base pairs, is key to its function in storing and transmitting genetic information.

DNA packaging is crucial for fitting the long molecule into cells. Nucleosomes, organization, and supercoiling all play important roles in compacting DNA while maintaining its accessibility for vital cellular processes.

DNA Structure

Double Helix and Base Pairing

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  • DNA forms a double helix structure consisting of two intertwined strands
  • Base pairing occurs between complementary nucleotides (adenine with thymine, guanine with cytosine)
  • Hydrogen bonds form between complementary bases, stabilizing the double helix
  • Two hydrogen bonds connect A-T pairs, while three hydrogen bonds connect G-C pairs
  • Complementary strands run antiparallel, with one strand running 5' to 3' and the other 3' to 5'
  • Base pair stacking contributes to the stability of the double helix through hydrophobic interactions

Structural Features of the Double Helix

  • Major groove and minor groove form along the length of the double helix
    • Major groove provides easier access for protein binding and interactions
    • Minor groove offers a narrower space for specific protein recognition
  • Phosphodiester bonds connect adjacent nucleotides within each strand
    • Forms between the 3' hydroxyl group of one and the 5' phosphate group of the next
    • Creates the sugar-phosphate backbone of DNA
  • Antiparallel strands result in asymmetric ends of the double helix
    • 5' end has a terminal phosphate group
    • 3' end has a terminal hydroxyl group

Chemical and Physical Properties

  • DNA molecule carries a negative charge due to phosphate groups in the backbone
  • Hydrophilic exterior and hydrophobic interior contribute to overall stability
  • Base stacking interactions provide additional stability to the double helix
  • Diameter of the DNA double helix measures approximately 2 nanometers
  • One complete turn of the helix contains about 10.5 base pairs in
  • Rise per base pair in B-DNA is approximately 0.34 nanometers

DNA Packaging

Nucleosome Structure and Function

  • Nucleosomes serve as the fundamental unit of DNA packaging in eukaryotic cells
  • Each consists of approximately 147 base pairs of DNA wrapped around a octamer
  • Histone octamer contains two copies each of histones H2A, H2B, H3, and H4
  • Linker DNA connects adjacent nucleosomes, ranging from 10 to 80 base pairs in length
  • Histone H1 binds to the linker DNA, further compacting the chromatin structure
  • Nucleosomes help regulate by controlling DNA accessibility

Chromatin Organization and Dynamics

  • Chromatin represents the complex of DNA and proteins in the nucleus
  • Primary structure of chromatin resembles a "beads on a string" appearance
  • Higher-order chromatin structures include the 30 nm fiber and more compact forms
  • refers to less condensed, transcriptionally active regions of chromatin
  • denotes highly condensed, transcriptionally inactive regions
  • Chromatin remodeling enzymes can alter nucleosome positioning and DNA accessibility
  • Histone modifications (methylation, acetylation, phosphorylation) influence chromatin structure and function

DNA Supercoiling and Topological Stress

  • Supercoiling occurs when DNA is under- or overwound, creating torsional stress
  • Negative supercoiling (underwinding) facilitates DNA strand separation for replication and transcription
  • Positive supercoiling (overwinding) can inhibit DNA-dependent processes
  • Topoisomerases regulate DNA supercoiling by introducing temporary breaks in the DNA
  • Type I topoisomerases cut one strand of DNA to relieve supercoiling
  • Type II topoisomerases cut both strands of DNA and pass another DNA segment through the break

DNA Conformations

B-DNA: The Most Common Form

  • B-DNA represents the predominant conformation of DNA under physiological conditions
  • Right-handed double helix with approximately 10.5 base pairs per turn
  • Major groove measures 22 Å wide and 12 Å deep
  • Minor groove measures 12 Å wide and 6 Å deep
  • Base pairs are nearly perpendicular to the helical axis
  • Hydration shell surrounds the DNA molecule, contributing to its stability

A-DNA: An Alternative Right-Handed Conformation

  • forms under dehydrating conditions or in some protein-DNA complexes
  • Right-handed double helix with approximately 11 base pairs per turn
  • Wider and shorter than B-DNA, with a more compact structure
  • Major groove is narrower and deeper compared to B-DNA
  • Minor groove is wider and shallower than in B-DNA
  • Base pairs are tilted with respect to the helical axis
  • Often observed in RNA-DNA hybrids and some protein-DNA interactions

Z-DNA: The Left-Handed Conformation

  • forms a left-handed double helix, unlike B-DNA and A-DNA
  • Occurs in sequences with alternating purine-pyrimidine bases (GC repeats)
  • Zigzag pattern of the sugar-phosphate backbone gives it its name
  • Approximately 12 base pairs per turn
  • Narrower than B-DNA, with a more elongated structure
  • Only one deep groove present, equivalent to the minor groove of B-DNA
  • Formation of Z-DNA can be induced by high salt concentrations or negative supercoiling
  • May play a role in gene regulation and genomic instability

Key Terms to Review (24)

A-DNA: A-DNA is a right-handed double helix form of DNA that is more compact and has a deeper major groove compared to B-DNA, which is the more common form of DNA found in cells. A-DNA typically forms under dehydrated conditions and plays a role in certain biological processes, making it an important variant in the overall understanding of DNA structure and organization.
Adenine-thymine pairing: Adenine-thymine pairing refers to the specific hydrogen bonding between the nitrogenous base adenine (A) and thymine (T) in DNA, forming a base pair. This pairing is crucial for the double helical structure of DNA and ensures accurate replication and transcription of genetic information. The complementarity of adenine and thymine is a fundamental aspect of DNA's stability and function, contributing to its role as the carrier of genetic information.
B-DNA: b-DNA is the most common form of DNA in living organisms, characterized by its right-handed helical structure. This form is essential for the proper storage and replication of genetic information, featuring two complementary strands that run antiparallel to each other, allowing base pairing between adenine-thymine and guanine-cytosine. The b-DNA structure plays a crucial role in DNA's stability and functionality, impacting processes like transcription and replication.
Chromatin: Chromatin is a complex of DNA and proteins found in the nucleus of eukaryotic cells, which plays a crucial role in the packaging of DNA into a more compact, organized structure. This structure is essential for fitting DNA into the nucleus and for regulating gene expression, DNA replication, and repair. Chromatin exists in two forms: euchromatin, which is loosely packed and associated with active transcription, and heterochromatin, which is tightly packed and generally inactive in transcription.
DNA Replication: DNA replication is the biological process by which a cell makes an identical copy of its DNA, ensuring that genetic information is accurately passed on during cell division. This process is essential for growth, development, and tissue repair, as it guarantees that each new cell receives the complete set of genetic instructions. It involves multiple steps and key enzymes that work together to unwind the DNA double helix, synthesize new strands, and proofread for errors.
DNA Transcription: DNA transcription is the process by which a segment of DNA is copied into RNA by the enzyme RNA polymerase. This process is essential for gene expression, as it converts the genetic information stored in DNA into a format that can be read and utilized to produce proteins. Transcription occurs in the cell nucleus and is a critical step in the central dogma of molecular biology, where DNA serves as the template for RNA synthesis.
Double helix: The double helix is the structure of DNA, consisting of two long strands that coil around each other, resembling a twisted ladder. This unique shape is essential for DNA's function in storing and transmitting genetic information, as it allows for the complementary base pairing that underlies the mechanisms of replication and transcription.
Euchromatin: Euchromatin is a less condensed form of chromatin that is associated with actively transcribed genes, allowing for easier access to DNA by the transcription machinery. This open structure contrasts with heterochromatin, which is tightly packed and typically transcriptionally inactive. Euchromatin plays a critical role in gene expression regulation, making it a key component of cellular processes involving DNA organization and epigenetic modifications.
Francis Crick: Francis Crick was a British molecular biologist, biophysicist, and neuroscientist who is best known for co-discovering the double helix structure of DNA alongside James Watson in 1953. His groundbreaking work has had a lasting impact on our understanding of DNA structure and organization, which is crucial for genetics and molecular biology.
Gel electrophoresis: Gel electrophoresis is a laboratory technique used to separate and analyze macromolecules, primarily nucleic acids and proteins, based on their size and charge. This method utilizes an electric field to drive the molecules through a gel matrix, where smaller fragments migrate faster than larger ones, enabling their identification and characterization. It's a crucial technique for understanding the structure and organization of DNA, as it allows for the visualization of DNA fragments after processes like restriction enzyme digestion or PCR amplification.
Gene expression: Gene expression is the process by which information encoded in a gene is translated into a functional product, typically a protein. This involves several steps including transcription, where DNA is converted to messenger RNA (mRNA), followed by translation, where mRNA is decoded to produce proteins. The regulation of gene expression ensures that genes are activated or silenced at the right times and in the right cell types, which is crucial for maintaining cellular functions and responding to environmental signals.
Genetic code: The genetic code is a set of rules that defines how the information encoded in DNA is translated into proteins, which are essential for the functioning of all living organisms. This code is based on sequences of nucleotides in DNA, where groups of three nucleotides, known as codons, correspond to specific amino acids that make up proteins. The genetic code is universal among almost all organisms, highlighting the shared evolutionary heritage of life.
Guanine-cytosine pairing: Guanine-cytosine pairing refers to the specific hydrogen bonding interaction between the nucleobase guanine and its complementary partner cytosine in the structure of DNA. This pairing is crucial for the stability of the DNA double helix and plays a key role in the accurate replication and transcription of genetic information.
Heterochromatin: Heterochromatin refers to a tightly packed form of DNA that is typically transcriptionally inactive, playing a crucial role in maintaining chromosomal structure and regulating gene expression. This dense packing makes it less accessible for transcription factors and RNA polymerase, which is essential for gene expression, thereby influencing cellular functions and development. Heterochromatin can be found at the centromeres and telomeres of chromosomes, providing structural support, while also being involved in epigenetic regulation.
Histone: Histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order DNA into structural units called nucleosomes. These proteins play a crucial role in DNA organization by helping to condense the long strands of DNA into a compact form, allowing for efficient storage and regulation of genetic information. Histones also participate in the regulation of gene expression through various post-translational modifications, impacting how tightly DNA is wound around them.
Hydrogen bond: A hydrogen bond is a weak, non-covalent attraction between a hydrogen atom covalently bonded to an electronegative atom and another electronegative atom. In the context of molecular biology, these bonds play a critical role in the structure and stability of DNA, influencing how base pairs interact and ultimately contributing to the double helix formation.
James Watson: James Watson is a molecular biologist and geneticist best known for co-discovering the structure of DNA in 1953 alongside Francis Crick. This landmark discovery has greatly influenced the field of biochemistry, providing insight into how genetic information is stored and transmitted, which is crucial for understanding biological processes at the molecular level.
Nucleosome: A nucleosome is the basic unit of DNA packaging in eukaryotic cells, consisting of a segment of DNA wrapped around a core of histone proteins. This structure plays a critical role in the organization of DNA, allowing it to be compacted into the chromatin structure that makes up chromosomes. The arrangement of nucleosomes influences gene expression and accessibility, thereby regulating various cellular processes.
Nucleotide: A nucleotide is the basic building block of nucleic acids, which are essential molecules in all living organisms. Each nucleotide consists of three components: a nitrogenous base, a five-carbon sugar, and one or more phosphate groups. These components come together to form DNA and RNA, playing critical roles in genetic information storage, transfer, and expression.
Phosphodiester bond: A phosphodiester bond is a type of covalent bond that links nucleotides together in a nucleic acid, forming the backbone of DNA and RNA. This bond occurs between the phosphate group of one nucleotide and the hydroxyl group of the sugar in another nucleotide, allowing for the formation of long, stable chains essential for the structure and function of genetic material.
Supercoiled DNA: Supercoiled DNA is a form of DNA that has been twisted or coiled to a greater extent than the relaxed double helix, resulting in a more compact structure. This supercoiling is crucial for the organization of DNA within cells, allowing long strands of DNA to fit into the confined space of the nucleus while also playing a key role in processes such as replication and transcription.
Topoisomerase: Topoisomerase is an enzyme that regulates the overwinding or underwinding of DNA by cutting the DNA strands, allowing them to rotate and rejoining them to relieve tension. This function is crucial during processes like DNA replication and transcription, where the double helix must unwind and stabilize for the genetic information to be accessed and utilized properly.
X-ray Crystallography: X-ray crystallography is a powerful technique used to determine the atomic and molecular structure of a crystal by diffracting X-rays through it. This method reveals the arrangement of atoms within the crystal, allowing scientists to understand the intricate details of biological macromolecules like proteins and nucleic acids, which is essential for studying their functions and interactions.
Z-DNA: Z-DNA is a left-handed helical form of DNA that is characterized by its zigzag backbone and a more elongated structure compared to the more common B-DNA. This unusual configuration can occur in regions of DNA with high GC content and is thought to play roles in gene regulation and chromatin structure, highlighting the diversity in DNA forms and their potential biological significance.
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