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Biological Chemistry I

🔬biological chemistry i review

11.2 DNA structure and organization

Last Updated on August 7, 2024

DNA structure and organization are fundamental to understanding genetic information. This topic explores the double helix, base pairing, and various helical forms. It also covers how DNA is packaged in cells, from nucleosomes to higher-order chromatin structures.

The physical properties of DNA, including supercoiling, denaturation, and renaturation, are crucial for its function. These concepts lay the groundwork for understanding DNA replication, transcription, and other processes involving nucleic acids.

DNA Structure

Helical Structure and Base Pairing

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  • DNA molecule consists of two antiparallel polynucleotide strands that wind around each other to form a right-handed double helix
  • Strands are held together by hydrogen bonds between complementary base pairs following Watson-Crick base pairing rules
    • Adenine (A) pairs with thymine (T) via two hydrogen bonds
    • Guanine (G) pairs with cytosine (C) via three hydrogen bonds
  • Sugar-phosphate backbones of the two strands are on the outside of the double helix, while the bases are stacked inside
  • Diameter of the double helix is approximately 20 Å (2 nm)

Grooves and Helical Forms

  • Double helix has two types of grooves: major groove and minor groove
    • Major groove is wider and deeper, allowing proteins to interact with the bases more easily
    • Minor groove is narrower and shallower
  • Different helical forms of DNA exist depending on environmental conditions and sequence composition
    • A-DNA is a right-handed double helix with a shorter, wider structure compared to B-DNA (found in dehydrated samples)
    • B-DNA is the most common form under physiological conditions, with 10.5 base pairs per helical turn
    • Z-DNA is a left-handed double helix that forms in regions with alternating purine-pyrimidine sequences (GC repeats)

DNA Packaging

Nucleosomes and Chromatin

  • In eukaryotic cells, DNA is packaged into chromatin to fit within the nucleus
  • Basic unit of chromatin is the nucleosome, which consists of:
    • Histone octamer core (two copies each of histones H2A, H2B, H3, and H4)
    • 147 base pairs of DNA wrapped around the histone octamer (~1.7 turns)
  • Linker DNA connects adjacent nucleosomes and is associated with histone H1
  • Nucleosomes are arranged like "beads on a string" to form the 10 nm chromatin fiber
  • Higher-order packaging of chromatin involves further compaction into the 30 nm fiber and higher-order structures

Supercoiling

  • DNA can undergo supercoiling, a process that introduces additional twists or writhes into the double helix
  • Positive supercoiling (overwinding) occurs when the double helix is twisted in the direction of the helix, increasing the number of turns
  • Negative supercoiling (underwinding) occurs when the double helix is twisted in the opposite direction, decreasing the number of turns
  • Supercoiling plays a crucial role in DNA packaging and can influence processes such as replication and transcription
  • Topoisomerases are enzymes that regulate the level of supercoiling by introducing or removing supercoils

DNA Properties

Denaturation and Renaturation

  • DNA denaturation is the process by which the double helix unwinds and separates into single strands
    • Caused by factors such as high temperature, extreme pH, or chemical denaturants (urea, formamide)
    • Hydrogen bonds between base pairs are disrupted, but the sugar-phosphate backbone remains intact
  • Renaturation (reannealing) is the process by which single-stranded DNA molecules reassociate to form a double helix
    • Occurs when denaturing conditions are removed and complementary strands find each other
    • Rate of renaturation depends on factors such as DNA concentration, sequence complexity, and ionic strength
  • Melting temperature (Tm) is the temperature at which 50% of the DNA is denatured
    • Depends on factors such as GC content (higher GC content leads to higher Tm) and salt concentration

Key Terms to Review (26)

Denaturation: Denaturation is the process in which proteins lose their native structure and function due to the disruption of non-covalent interactions and the unfolding of their secondary, tertiary, or quaternary structures. This alteration can occur due to various factors such as temperature changes, pH fluctuations, or exposure to chemicals. The loss of structure directly affects a protein's ability to perform its biological functions, leading to potential implications in protein classification, stability, and even nucleic acid organization.
Hydrogen Bonds: Hydrogen bonds are weak attractions that occur between a hydrogen atom covalently bonded to an electronegative atom and another electronegative atom. These interactions are crucial for maintaining the structure and stability of biomolecules, influencing the folding of proteins, the formation of protein complexes, and the overall organization of nucleic acids.
Transcription: Transcription is the biological process where the genetic information encoded in DNA is copied into messenger RNA (mRNA). This process is crucial because it allows the information stored in DNA to be converted into a form that can be translated into proteins, which perform essential functions in cells. During transcription, RNA polymerase synthesizes a complementary RNA strand using one of the DNA strands as a template, making it a fundamental step in gene expression.
Linker dna: Linker DNA refers to the short segments of DNA that connect adjacent nucleosome cores in eukaryotic chromatin. These segments play a crucial role in the overall structure and organization of DNA within the nucleus, helping to maintain the higher-order folding of chromatin necessary for efficient gene regulation and expression.
Topoisomerases: Topoisomerases are enzymes that regulate the overwinding or underwinding of DNA strands during processes like replication and transcription. They are essential for maintaining the structural integrity of DNA by introducing or removing supercoils, which helps prevent tangling and ensures proper accessibility of the genetic material for various cellular functions.
10 nm chromatin fiber: The 10 nm chromatin fiber is a fundamental structural unit of chromatin, consisting of DNA wrapped around histone proteins, creating a bead-like appearance known as nucleosomes. This fiber represents the first level of DNA packaging in eukaryotic cells, facilitating the compaction of DNA to fit within the nucleus while still allowing for accessibility during processes like transcription and replication.
Dna polymerase: DNA polymerase is an enzyme that synthesizes new DNA strands by adding nucleotides to a pre-existing chain during DNA replication. It plays a crucial role in ensuring accurate duplication of the genetic material, as it not only catalyzes the polymerization process but also possesses proofreading capabilities to maintain fidelity in DNA synthesis.
Replication: Replication is the biological process by which a cell makes an identical copy of its DNA. This process is crucial for cell division and ensures that each daughter cell receives the same genetic information as the parent cell. Replication is highly regulated and involves multiple enzymes and proteins to maintain the accuracy of the genetic code.
30 nm fiber: The 30 nm fiber is a structural form of chromatin that plays a critical role in the packaging of DNA within the nucleus. This fiber consists of nucleosomes, which are formed by DNA wrapped around histone proteins, further coiling and folding to achieve a more compact organization of genetic material, allowing for efficient storage and regulation of DNA during cellular processes.
Minor groove: The minor groove is a structural feature of the DNA double helix that occurs where the two strands of DNA are closer together, creating a narrower opening compared to the wider major groove. This configuration allows for specific interactions with proteins and other molecules, playing a crucial role in DNA recognition and binding. The geometry of the minor groove contributes to the overall stability and functionality of the DNA molecule, influencing how genes are expressed and regulated.
Major groove: The major groove is one of the two distinct grooves found in the double helix structure of DNA, which plays a crucial role in molecular interactions. This groove is wider and deeper compared to the minor groove, allowing proteins and other molecules to access the DNA for processes such as transcription and replication. The shape and size of the major groove provide specific binding sites for regulatory proteins that recognize particular DNA sequences.
Histone octamer: A histone octamer is a protein complex composed of eight histone proteins that play a critical role in the organization and packaging of DNA into chromatin. This structure forms the core around which DNA winds, allowing for the compact storage of genetic material within the nucleus of eukaryotic cells. The histone octamer is essential for the regulation of gene expression and the accessibility of DNA for transcription and replication.
Z-dna: Z-DNA is a left-handed helical form of DNA that differs from the more common right-handed double helix known as B-DNA. This unusual structure is characterized by a zigzag appearance and is thought to play a role in biological processes such as gene regulation and DNA packaging.
Watson-Crick Base Pairing: Watson-Crick base pairing refers to the specific hydrogen bonding between nucleotide bases in DNA, where adenine (A) pairs with thymine (T) and guanine (G) pairs with cytosine (C). This pairing is fundamental to the double-helix structure of DNA, ensuring accurate replication and transcription processes by maintaining complementary sequences between the two strands.
Base pairing: Base pairing refers to the specific hydrogen bonding between complementary nitrogenous bases in nucleic acids, primarily DNA and RNA. This essential interaction forms the basis for the double helical structure of DNA, where adenine pairs with thymine (or uracil in RNA) and cytosine pairs with guanine. Base pairing is crucial for processes such as DNA replication and transcription, ensuring that genetic information is accurately passed on and expressed.
A-DNA: a-DNA is a right-handed helical form of DNA that is more compact than the common B-DNA structure. It typically forms under dehydrated conditions and features a wider diameter, which affects the way genetic information is stored and accessed within cellular processes. This form of DNA is less stable than B-DNA and is usually not found in cells under normal physiological conditions, but it plays a role in specific environments or when interacting with certain proteins.
Supercoiling: Supercoiling refers to the twisting and winding of the DNA double helix beyond its normal relaxed state. This phenomenon is crucial for the compact organization of DNA within the cell, allowing long strands of DNA to fit into small cellular spaces. Supercoiling also plays a significant role in various biological processes, including DNA replication and transcription, by affecting the accessibility of the DNA for these essential functions.
Renaturation: Renaturation refers to the process by which denatured molecules, particularly nucleic acids and proteins, regain their original structure and function after being subjected to conditions that disrupt their native state. In the context of DNA, this is especially significant as it involves the re-annealing of separated strands of DNA, allowing them to restore their double helix structure and biological activity.
B-DNA: b-DNA is the most common form of DNA in biological systems, characterized by its right-handed double helix structure. This conformation features two strands running antiparallel to each other, with the bases oriented inward, allowing for specific base pairing that is essential for the stability and function of genetic material. The structure supports the overall organization and packaging of DNA within cells.
Double helix: The double helix is the structural configuration of DNA, consisting of two intertwined strands that resemble a twisted ladder. Each strand is composed of nucleotides, which include a sugar, phosphate group, and a nitrogenous base. The double helix structure allows for the stable storage of genetic information while providing mechanisms for replication and transcription.
Chromatin: Chromatin is a complex of DNA and proteins found in the nucleus of eukaryotic cells that serves to package and organize genetic material. It plays a crucial role in gene regulation, DNA replication, and cell division, by condensing DNA into a more compact form during cell division while allowing access to DNA for transcription when needed.
Nucleosome: A nucleosome is the fundamental unit of DNA packaging in eukaryotic cells, consisting of a segment of DNA wrapped around a core of histone proteins. This structure helps to compact and organize DNA within the nucleus, playing a crucial role in gene regulation and accessibility. By forming higher-order structures, nucleosomes enable the efficient storage and management of genetic information.
Guanine: Guanine is a nitrogenous base that is one of the four primary components of nucleotides, which are the building blocks of DNA and RNA. It plays a critical role in encoding genetic information and pairs specifically with cytosine during the formation of nucleic acid structures, establishing the fundamental base pairing that is essential for DNA stability and replication.
Thymine: Thymine is one of the four main nucleobases in the nucleic acid of DNA, categorized as a pyrimidine. It pairs specifically with adenine through two hydrogen bonds, contributing to the double-helix structure of DNA and playing a vital role in the storage and transmission of genetic information.
Cytosine: Cytosine is one of the four primary nitrogenous bases found in nucleotides, which are the building blocks of nucleic acids like DNA and RNA. It plays a critical role in encoding genetic information by pairing specifically with guanine through hydrogen bonds, ensuring the stability of the DNA double helix structure. Cytosine is also involved in various biochemical processes, including the synthesis of RNA and the regulation of gene expression.
Adenine: Adenine is a nitrogenous base that is one of the fundamental building blocks of nucleotides, which are the structural units of nucleic acids like DNA and RNA. It plays a crucial role in storing and transferring genetic information, forming base pairs with thymine in DNA and with uracil in RNA, and is also a component of important biomolecules such as ATP, which is essential for energy transfer in cells.