神奇的设计-为什么遗传信息载体DNA采取B型构象？

已确认的DNA 的不同构象

- Structural Integrity: 

   Both base stacking and hydrogen bonding contribute to the overall structural integrity of DNA. Mutations that weaken these interactions can lead to an increased likelihood of DNA strand breaks, replication errors, or even cancerous transformations.

A. DNA 构象类型

  The overall characteristics of different DNA structures, including the double helix, Z-DNA, G-quadruplex (G-stranded DNA), triplex DNA, and hairpin structures:

 1. DNA Double Helix (B-DNA)

- **Structure**: Right-handed helical structure, consisting of two antiparallel strands wound around each other.

- **Base Pairing**: Adenine pairs with thymine (A-T) via two hydrogen bonds, and guanine pairs with cytosine (G-C) via three hydrogen bonds.

- **Characteristics**:

  - Approximately 10.5 base pairs per turn.

  - Major and minor grooves facilitate protein binding and recognition.

  - Most stable and common form under physiological conditions, essential for genetic information storage and replication.

2. Z-DNA

- **Structure**: Left-handed helical structure with a zigzag backbone.

- **Base Pairing**: Similar to B-DNA but allows for syn and anti conformations of bases.

- **Characteristics**:

  - Approximately 12 base pairs per turn.

  - Formed under high salt concentrations or in sequences rich in alternating purines and pyrimidines (e.g., GCGCGC).

  - Associated with gene regulation and may respond to cellular stress, influencing transcriptional activity.

 3. G-Quadruplex (G-stranded DNA)

- **Structure**: Composed of four guanine bases that form a square planar arrangement known as a G-tetrad.

- **Formation**: Stabilized by Hoogsteen hydrogen bonding and often requires metal ions (like potassium) for stability.

- **Characteristics**:

  - Can exist in various topologies, including parallel, anti-parallel, or hybrid forms.

  - Found in guanine-rich regions such as telomeres and regulatory sequences of genes.

  - Implicated in gene regulation, telomere maintenance, and cancer biology.

 4. Triplex DNA

- **Structure**: Composed of three strands: two regular strands (like B-DNA) and a third strand that binds in the major groove.

- **Base Pairing**: The third strand can form Hoogsteen or reverse-Hoogsteen hydrogen bonds with the bases of the double helix.

- **Characteristics**:

  - Can stabilize specific sequences and influence gene expression.

  - Often found in regions of DNA that are regulatory or involved in chromatin structure.

  - May play roles in genetic regulation and therapeutic applications, such as gene targeting.

5. Hairpin Structures

- **Structure**: Formed when a single strand of DNA folds back on itself, creating a loop with paired bases.

- **Base Pairing**: Internal base pairing occurs within the same strand, creating a double-stranded region at the loop's base.

- **Characteristics**:

  - Common in single-stranded regions, such as during DNA replication or in certain RNA structures.

  - Can serve as recognition sites for proteins, affect stability, and play roles in genetic regulation.

  - Frequently observed in the context of DNA and RNA processing, such as in the formation of secondary structures during transcription.

### Summary

- **B-DNA** is the standard double helix essential for genetic storage.

- **Z-DNA** is a less common left-handed form that may influence gene regulation.

- **G-quadruplexes** are specialized guanine-rich structures implicated in telomere maintenance and regulation.

- **Triplex DNA** allows for additional base pairing, potentially regulating gene expression.

- **Hairpin structures** occur when single strands fold back on themselves, playing roles in DNA and RNA function.

These diverse DNA structures highlight the complexity of genetic material and its functional versatility in biological processes.

B. 只有B型构象能量最低，最稳定

Energy Comparison 

The stability and energy characteristics of various DNA structures, including the double helix (B-DNA), Z-DNA, G-quadruplex (G-stranded DNA), triplex DNA, and hairpins, vary significantly based on their structural features and the types of interactions involved. 

Overview of each type of conformers concerning energy and stability:

### 1. DNA Double Helix (B-DNA)

- **Stability**: Highly stable under physiological conditions.

- **Energy**: The stability comes from:

  - **Base Pairing**: A-T and G-C pairs contribute to stability through hydrogen bonds.

  - **Base Stacking**: Strong π-π stacking interactions between adjacent bases provide significant stabilization.

  - **Hydrophobic Interactions**: Nonpolar bases are shielded from the aqueous environment, enhancing stability.

- **Factors Affecting Stability**: Temperature, ionic strength, and pH can influence the stability of B-DNA.

### 2. Z-DNA

- **Stability**: Less stable than B-DNA but can be stabilized under specific conditions.

- **Energy**: The unique left-handed helical structure and zigzag backbone confer specific stability:

  - **Base Pairing**: Similar hydrogen bonding as in B-DNA, but the structure allows for different pairing conformations.

  - **Environmental Conditions**: Stabilized by high salt concentrations or supercoiling, which promotes its formation.

- **Factors Affecting Stability**: Sequence context (e.g., alternating purines and pyrimidines) and external stress can influence Z-DNA formation.

### 3. G-Quadruplex (G-stranded DNA)

- **Stability**: Highly stable due to specific structural features.

- **Energy**: Stability arises from:

  - **Guanine Tetrads**: Four guanine bases form a G-tetrad, stabilized by Hoogsteen hydrogen bonds.

  - **Metal Ions**: Presence of cations (like K⁺ or Na⁺) enhances stability by stabilizing the G-quadruplex structure.

  - **Base Stacking**: The stacked G-tetrads contribute to overall stability.

- **Factors Affecting Stability**: The stability of G-quadruplexes is influenced by the presence of metal ions, temperature, and the surrounding nucleotide sequence.

### 4. Triplex DNA

- **Stability**: Moderate stability, influenced by the sequence and type of base pairing.

- **Energy**: Stability mechanisms include:

  - **Hoogsteen Base Pairing**: The third strand interacts with the double helix, contributing to stability but generally weaker than standard Watson-Crick pairings.

  - **Structural Context**: Triplex DNA is often found in regions that can tolerate structural distortions.

- **Factors Affecting Stability**: pH, ionic strength, and the presence of specific sequences can significantly impact triplex stability.

### 5. Hairpin Structures

- **Stability**: Stability can vary based on the length of the loop and the degree of base pairing.

- **Energy**: Stability is derived from:

  - **Internal Base Pairing**: Base pairs in the stem contribute significantly to stability.

  - **Loop Size**: Short loops are generally more stable than longer loops due to reduced steric strain.

- **Factors Affecting Stability**: Temperature, loop length, and the sequence of the stem can influence the stability of hairpin structures.

### Summary of Energy and Stability

- **B-DNA** is the most stable and energetically favorable under normal conditions due to strong base pairing and stacking.

- **Z-DNA** is less stable overall but can be stabilized under specific conditions, particularly in sequences that promote its formation.

- **G-quadruplexes** exhibit high stability, particularly in guanine-rich regions, and are influenced by metal ions.

- **Triplex DNA** has moderate stability, dependent on the specific sequence and environmental conditions.

- **Hairpins** can be stable, especially with short loops and strong base pairing in the stem, but their stability is influenced by various factors.

C.碱基的改变对DNA B 构象的影响

a. Effects on Base Stacking

1. **Type of change **:

   * **Substitutions**: Replacing one base with another (e.g., A to G) can alter the stacking interactions. For instance, purine-purine or pyrimidine-pyrimidine stacking may be less favorable than purine-pyrimidine stacking, potentially destabilizing the helix.

   * **Insertions/Deletions**: These can disrupt the regular helical structure, leading to local distortions in base stacking. This can create stress points in the DNA, affecting its overall stability.

2. **Impact on Stability**:

   * Changes in base identity can lead to different stacking energies, influencing how tightly bases interact with their neighbors. Weaker stacking interactions can make the DNA more susceptible to denaturation, especially under stress conditions.

b. Effects on Hydrogen Bonding

1. **Type of Change**:

   * **Substitutions**: Changes of base that can affect the specificity and number of hydrogen bonds. For example, a change from adenine to cytosine alters the A-T pair (2 hydrogen bonds) to a C-G pair (3 hydrogen bonds), potentially increasing stability in that region.

   * **Mismatches**: Changes that may introduce mismatches (e.g., A paired with C), leading to non-canonical hydrogen bonding. This can destabilize the double helix and might lead to errors during replication.

2. **Impact on Fidelity**:

   * Altered hydrogen bonding can affect the fidelity of DNA replication and transcription. Mismatches might lead to mispairing during DNA synthesis, increasing the mutation rate.

Summary

- **Functional Implications**: Changes in base stacking and hydrogen bonding can influence gene expression and regulation, potentially leading to phenotypic variations or diseases.

In summary, Changes of bases in the DNA sequence adopted in a B conformation are thought to be mutations, which can disrupt both base stacking and hydrogen bonding, impacting the stability and functionality of DNA, with varying consequences depending on the nature and location of the mutation.

D. 修复机制视非B为“异类”

请结合以下章节形成系统：

题目

The Gratuitous Repair on Undamaged DNA Misfold 

Written By

Xuefeng Pan, Peng Xiao, Hongqun Li, Dongxu Zhao and Fei Duan

Submitted: 19 November 2010 Published: 07 November 2011

DOI: 10.5772/22441 https://www.intechopen.com/chapters/23161