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Questions and Answers
Covalent bonds hold the sugar-phosphate backbone of DNA together.
True
The two strands of DNA run in the same direction.
False
A and G are complementary base pairs in DNA.
False
A GC-rich region of DNA is less thermodynamically stable than an AT-rich region.
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The sequence of DNA base pairs is usually written from 5' to 3'.
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Base stacking refers to hydrogen bonding between DNA bases.
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The edges of the DNA bases are exposed to the environment in the major and minor grooves.
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The 3' end of a DNA strand has a free phosphate group.
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Proteins are produced directly from the DNA without any intermediary.
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The human genome contains approximately 21,000 genes.
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DNA is composed of two strands arranged in a parallel orientation.
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The Central Dogma of molecular biology includes transmission of information from DNA to RNA to protein.
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Functional RNA molecules, such as tRNA, are produced from genes.
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Histone modification is a mechanism for regulating gene expression.
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The sugar-phosphate backbone of DNA is on the interior of the molecule.
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James Watson and Francis Crick proposed the structure of DNA in 1953.
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Each human cell contains approximately $3.2 x 10^9$ base pairs (bp) distributed across 46 chromosomes.
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Euchromatin is highly compact and does not allow transcription to occur.
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Histones are the major proteins involved in the organization of chromatin.
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Each nucleosome consists of 160 to 240 bp of DNA and contains only H3 and H4 histones.
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H1 histone is located inside the core particle of the nucleosome.
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The '30 nm fibre' is a higher-level structure formed by the coiling of nucleosomes.
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Uncomplexed 'naked' DNA is a normal structure found in human cells.
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In fully condensed chromosomes, the length of DNA is reduced by about 10,000-fold.
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Heterochromatin is characterized by DNA that is actively transcribed.
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Euchromatin allows for easier access to transcription factors and can be transcribed into RNA.
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Methylation of nucleotide bases promotes relaxation of chromatin structure.
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Histone Acetyl Transferases (HATs) are activated by environmental cues to promote gene expression.
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Histone Deacetylases (HDACs) are responsible for promoting transcription when a gene's expression is not required.
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Vorinostat is an HDAC inhibitor that has been approved for treating cutaneous T-cell lymphoma.
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Condensed chromatin is associated with the activation of silenced genes.
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The compaction ratio of chromatin can be 1:10,000.
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DNA consists of three polynucleotide strands wound around a common axis.
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The four different deoxyribonucleotides found in DNA are adenine, guanine, cytosine, and thymine.
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The sugar-phosphate backbone of DNA is located on the interior of the molecule.
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Histone modification can influence the structure of chromatin and gene expression.
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Functional RNA molecules are never produced directly from genes.
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Each human cell contains approximately $3.2 x 10^9$ base pairs of DNA.
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The primary structure of DNA was discovered by Rosalind Franklin and Maurice Wilkins.
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Euchromatin is typically associated with gene transcription and less compact structure.
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Heterochromatin is characterized by being highly diffuse and allowing transcription.
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The nucleosome consists of approximately 200 base pairs of DNA and is associated with multiple histone proteins.
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The '30 nm fibre' refers to a structural organization of nucleosomes that results in a 40-fold reduction in the length of DNA.
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All histones contain an equal proportion of positively charged amino acids.
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The core particle of the nucleosome is formed by an octamer of histones accommodating H1 on the inside.
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Naked DNA is the normal form of DNA found in human cells.
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Each type of histone has a mass ranging from 11 to 21 kDa.
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The structure of chromatin is essential for compacting DNA into the nucleus of the cell.
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A region of DNA that is rich in GC pairs has lower thermodynamic stability compared to AT-rich regions.
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The sugar-phosphate backbone of DNA is composed of alternating sugar and phosphate groups held together by phosphodiester bonds.
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The DNA strands run in a parallel orientation to each other.
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Heterochromatin is characterized by DNA that is supercoiled and allows for gene transcription.
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Watson-Crick base pairing allows for the specific pairing of bases A with G and C with T.
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Acetylation of histone residues leads to a more compact chromatin structure.
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Certain regions of DNA, such as telomeres and centromeres, are usually found in euchromatin form.
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The major and minor grooves on the DNA molecule result from the arrangement of the sugar-phosphate backbone.
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Hydrogen bonds are the strongest non-covalent forces stabilizing the DNA structure.
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Histone Deacetylases (HDACs) are activated when the expression of a gene is required.
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The activation of silenced genes occurs during the decondensation of chromatin.
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Complementary base pairing means that one strand of DNA will have the same sequence as the other strand.
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The directionality of DNA is critical as it determines how genetic information is read and replicated.
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Vorinostat has only demonstrated efficacy in treating cutaneous T-cell lymphoma and not any solid malignancies.
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Environmental cues stimulate Histone Acetyl Transferases (HATs) to unwind DNA for gene expression.
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Methylation of nucleotide bases generally leads to relaxation of chromatin structure.
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The structure of DNA consists of three polynucleotide strands wound around a common axis.
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Functional RNA molecules can be produced directly from genes.
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The sugar-phosphate backbone of DNA is located externally and protects the base pairs on the interior.
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Euchromatin is characterized by being highly compact and does not allow transcription.
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The four different deoxyribonucleotides in DNA are adenine, guanine, cytosine, and uracil.
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Methylation of nucleotide bases is associated with the compaction of chromatin structure.
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The '30 nm fibre' results from the coiling of nucleosomes and represents a level of chromatin structure.
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Condensed chromatin is associated with gene activation.
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An adenine base pairs with a cytosine base in DNA.
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The structure of DNA includes covalent bonds only within the nucleotides and not along the backbone.
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A region with high GC content is less stable than a region with high AT content.
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The 5' end of a DNA strand has a free hydroxyl group at carbon C-3 of the last 2'-deoxyribose.
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The complementary base-pairing in DNA results in two hydrogen bonds between guanine and adenine.
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Base stacking is considered a non-covalent force that contributes to the DNA structure.
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The sugar-phosphate backbone of DNA is located on the interior of the DNA double helix.
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DNA base sequences are written from 5' to 3' to reflect their structural orientation.
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Lysines, being positively charged, neutralize their charge when acetylated, leading to looser DNA structure.
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Naked DNA is the predominant form of DNA found inside human cells.
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Heterochromatin is known to be actively transcribed, allowing for high gene expression.
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Histones H2A, H2B, H3, and H4 are present in pairs within each nucleosome.
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Vorinostat is an FDA-approved treatment for solid malignancies but not for hematological cancers.
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The 30 nm fibre represents a stage where the DNA is reduced by approximately 40-fold in length.
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Methylation of nucleotide bases in DNA aids in gene expression by relaxing the chromatin structure.
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Heterochromatin allows transcription to occur and is less compact than euchromatin.
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The structure of chromatin is irrelevant in regulating transcription as it does not affect DNA accessibility.
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Each nucleosome is associated with a single molecule of H1 histone located at its core.
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Condensed chromatin is associated with the deactivation of silenced genes.
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The core particle of a nucleosome is formed by an octamer of 4 types of histones.
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Acetylation of histones is primarily triggered by cellular cues to enhance gene expression.
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Certain regions of DNA, such as telomeres and centromeres, are permanently in euchromatin form.
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The overall structure of nucleosomes contributes to a reduction in DNA length by approximately 10-fold in fully condensed chromosomes.
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Nucleosomes are visualized as 'beads on a string' under an electron microscope.
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Study Notes
DNA Structure and Function
- Genes determine the structure and function of cells.
- Genes are segments of DNA that direct protein synthesis.
- The entire set of DNA is called the genome.
- The human genome contains approximately 21,000 genes.
Central Dogma of Molecular Biology
- DNA is transcribed to RNA.
- RNA is translated into proteins.
DNA Structure
- DNA is a double helix with two anti-parallel polynucleotide strands.
- The sugar-phosphate backbone is on the exterior.
- Purine and pyrimidine bases are on the interior.
- Bases pair complementarily: adenine (A) with thymine (T) and guanine (G) with cytosine (C).
DNA Backbone
- The sugar-phosphate backbone is held together by covalent bonds.
- The bonds are 3' to 5' phosphodiester bonds.
Directionality in DNA
- Each DNA strand has distinct directionality.
- One end of a DNA strand ends with a free hydroxyl or phosphate group on the 5' carbon of the last deoxyribose (5' end).
- The other end ends with a free hydroxyl or phosphate group on the 3' carbon of the last deoxyribose (3' end).
Watson-Crick Base Pairing
- Adenine (A) forms two hydrogen bonds with thymine (T).
- Guanine (G) forms three hydrogen bonds with cytosine (C).
Major and Minor Grooves
- The sugar-phosphate backbones create two grooves on the surface of the DNA molecule: the major groove and the minor groove.
- The edges of the bases are exposed to the environment in the grooves.
Complementarity
- The two DNA strands are complementary because of specific base pairing.
- The sequence of bases along one strand reflects the other strand.
- Genetic information is stored in the sequence of bases.
- DNA sequences are written from 5' to 3' by convention.
Forces Holding DNA Together
- Covalent Bonds: Covalent bonds within nucleotides and phosphodiester bonds along the backbone
-
Non-Covalent Bonds:
- Base stacking: van der Waals interaction between the stacked base pairs is the strongest non-covalent force.
- Hydrogen bonding: G-C has 3 hydrogen bonds. A-T has 2 hydrogen bonds.
- GC-rich regions are thermodynamically more stable.
Higher Order Structure of Chromosomes
- Each human cell contains a vast amount of DNA: approximately 3.2 billion base pairs in 23 chromosomes.
- The average chromosome length is 3.8 cm.
- Diploid cells contain 46 chromosomes, totaling ~1.8 meters of DNA.
Chromatin Structure and Organization
- DNA is complexed with proteins to compact it into structures for cell division.
- This complex is called chromatin.
- Chromatin consists of approximately 50% DNA and 50% protein by weight.
Types of Chromatin
- Heterochromatin: Highly compacted, inactive DNA. No transcription occurs.
- Euchromatin: Diffuse, active DNA. Transcription is possible.
Histones
- Histones are the main proteins involved in chromatin organization.
- There are five types of histones: H1, H2A, H2B, H3, and H4.
- All histones have a high content of positively charged amino acids (lysine and arginine) which allows them to interact with negatively charged DNA.
The Nucleosome
- The basic repeating structural unit of chromatin is the nucleosome.
- Each nucleosome consists of:
- ~200 bp of DNA (160-240 bp)
- 2 molecules each of H2A, H2B, H3, and H4
- 1 molecule of H1 associated with the outside of the core particle
- DNA between nucleosomes is called linker DNA.
Nucleosome Structure
- Histones (except H1) form an octamer core particle.
- ~140 bp of DNA wraps around the octamer forming ~1.75 turns of a left-handed superhelix.
Higher Levels of Chromosome Structure
- Nucleosomes coil to form a 30 nm fiber called the "30 nm fiber".
- This structure reduces the length of DNA by 40-fold.
- Solenoid loops are anchored to scaffold proteins, further reducing DNA length and ultimately forming chromosomes.
Compaction of Chromatin
- Basic helix → Nucleosome → Chromatin → Scaffold → Loops → Chromosome
- Compaction is 1:10,000.
Classification of Chromatin
- Heterochromatin: Supercoiled and condensed DNA. Genes in heterochromatin are not transcribed.
- Euchromatin: Accessible to transcription factors and transcribed into RNA.
Modifications of Chromatin
- Methylation of nucleotide bases promotes compaction.
- Acetylation of specific histone residues promotes relaxation.
- These modifications are important in gene expression regulation.
Role of Chromatin Structure in Regulating Transcription
- Lysine residues on histones are positively charged.
- This charge interacts with negatively charged DNA on neighboring nucleosomes, causing DNA condensation.
- Acetylation neutralizes the positive charge on lysines.
- Acetylation promotes looser DNA structure and aids transcription.
- Histone Acetyl Transferases (HATs) activate gene expression by unwinding DNA.
- Histone Deacetlyases (HDACs) repress gene expression by condensing DNA.
Clinical Notes
- Condensed chromatin can silence tumor suppressor genes, leading to cancer.
- HDAC inhibitors (such as Vorinostat) are approved for cutaneous T-cell lymphoma (CTCL).
- HDAC inhibitors are also being investigated for solid malignancies in combination with chemotherapy.
The Central Dogma
- Explains the flow of genetic information in biology.
- Genes are sections of DNA that instruct the creation of a protein.
- The entire set of DNA in an organism is its genome.
DNA Structure
- Discovered by James Watson and Francis Crick in 1953.
- A double helix formed by two antiparallel strands.
- Sugar-phosphate backbone on the exterior of the helix.
- Bases (Adenine, Thymine, Guanine, Cytosine) are on the inside.
- Bases pair via hydrogen bonding: A with T, G with C.
DNA Backbone
- Sugar-phosphate backbone formed by covalent bonds.
- Phosphodiester bond present between phosphate group of one nucleotide and the hydroxyl group of the next.
Directionality of DNA
- Each strand has a defined direction.
- The 5’ end has a free phosphate group.
- The 3’ end has a free hydroxyl group.
- Strands run in antiparallel orientation.
Major and Minor Grooves
- DNA has major and minor grooves caused by the sugar-phosphate backbone.
- The grooves allow proteins to recognize and bind to specific DNA sequences.
Complementarity
- The sequence of one strand determines the sequence of its complementary strand.
- DNA sequences are written from 5’ to 3’ by convention.
Forces Holding DNA Together
- Covalent bonds are the strongest, within nucleotides and along the backbone.
-
Non-covalent bonds:
- Base stacking through van der Waals interactions between the stacked bases.
-
Hydrogen bond between complementary bases:
- A-T has 2 hydrogen bonds.
- G-C has 3 hydrogen bonds.
Higher Order Structure of Chromosomes
- Human DNA is extremely long (1.8 meters) compared to the size of a cell.
- Chromatin is a complex of DNA and protein.
- Chromatin helps organize, fold, and compact the DNA.
Histones
- Major proteins responsible for chromatin organization.
- Five types: H1, H2A, H2B, H3, H4.
- Rich in positively charged amino acids, allowing them to interact with negatively charged DNA.
The Nucleosome
- The basic structural unit of chromatin.
- Consists of:
- ~200 bp DNA
- Octamer of histone proteins (two each of H2A, H2B, H3, H4).
- H1 histone associated on the outside.
- DNA wraps around the histone octamer.
Higher Levels of Chromosome Structure
- Nucleosomes coil to form a 30 nm fiber called the “solenoid.”
- This further condenses through looping and attachment to scaffold proteins.
- The final structure is a highly compact chromosome.
Classification of Chromatin
- Heterochromatin is dense and inactive, genes are not transcribed.
- Euchromatin is loose and active, genes can be transcribed.
- Methylation of DNA promotes condensation.
- Acetylation of histone tails promotes relaxation.
Role of Chromatin Structure in Regulating Transcription
- Histone acetylation promotes gene expression by relaxing DNA structure.
- Histone deacetylation represses gene expression by condensing DNA.
- Acetylation neutralizes the positive charge of lysine, reducing DNA compaction.
- Histone Acetyl Transferases (HATs) unwind DNA.
- Histone Deacetylases (HDACs) condense DNA.
Clinical Notes
- HDAC inhibitors, like vorinostat, are used in cancer treatment.
- Vorinostat targets histone deacetylases to activate tumor suppressor genes and induce cell death.
Information Processing in Biology
- Proteins are the building blocks of cells and determine their structure and function.
- A gene is a section of DNA that directs the synthesis of a protein.
- The human genome contains approximately 21,000 genes.
- The central dogma of molecular biology, proposed by Francis Crick in 1956, outlines the flow of genetic information from DNA to RNA to protein.
DNA Structure
- DNA is a long, thread-like molecule composed of two strands.
- Each strand is made up of four different deoxyribonucleotides: adenine (A), thymine (T), guanine (G), and cytosine (C).
- The two strands are wound around a common axis in an anti-parallel orientation.
- The sugar-phosphate backbone is on the exterior of the molecule, while the purine and pyrimidine bases are on the interior.
- Complementary base pairing occurs between adenine and thymine (A-T), and guanine and cytosine (G-C), held together by hydrogen bonds.
DNA Backbone
- The sugar-phosphate backbone is held together by covalent bonds, specifically 3' to 5' phosphodiester bonds.
Directionality in DNA
- Each DNA strand has a distinct directionality, with one end designated as 5' and the other as 3'.
- The 5' end has a free hydroxyl or phosphate group at carbon C-5 of the last deoxyribose, while the 3' end has a free hydroxyl or phosphate group at carbon C-3 of the last deoxyribose.
Watson-Crick Base Pairing
- The specific base pairing between A-T and G-C is critical for the structure and function of DNA.
Major and Minor Grooves
- The sugar-phosphate backbones create major and minor grooves on the surface of the DNA molecule.
- The edges of the DNA bases are exposed to the environment in these grooves.
Complementarity in DNA
- The two DNA strands are complementary, meaning the sequence of bases on one strand reflects that of the other.
- Genetic information is stored in the sequence of bases, and by convention, DNA sequences are written from 5' to 3'.
Forces Holding DNA Together
- Covalent bonds, including those within nucleotides and phosphodiester bonds in the backbone, are the strongest forces maintaining DNA structure.
- Non-covalent interactions include base stacking, which is the strongest non-covalent force, and hydrogen bonding between base pairs (A-T forming 2 hydrogen bonds and G-C forming 3 hydrogen bonds).
- Regions of DNA with a higher GC content are more thermodynamically stable due to the three hydrogen bonds between G and C.
Higher Order Structure of Chromosomes
- The enormous amount of DNA in human cells (approximately 3.2 x 10^9 base pairs) requires complex organization to fit within the cell.
- This organization is achieved through the formation of chromatin, a complex of DNA and proteins.
Chromatin Structure and Organization
- Chromatin consists of approximately 50% DNA and 50% protein by weight.
- It exists in two states: heterochromatin (highly compact, inactive) and euchromatin (diffuse, active transcription).
- Uncomplexed 'naked' DNA is abnormal in the cell.
Histones
- Histones are the major proteins involved in chromatin organization.
- There are five types of histones: H1, H2A, H2B, H3, and H4.
- They are rich in positively charged amino acids, allowing them to interact with negatively charged DNA.
The Nucleosome
- The nucleosome is the basic repeating structural unit of chromatin.
- Each nucleosome consists of:
- Approximately 200 base pairs of DNA wrapped around a histone octamer core.
- Two molecules each of H2A, H2B, H3, and H4.
- One molecule of H1 associated on the outside of the core particle.
- The DNA between nucleosomes is called linker DNA.
Higher Levels of Chromosome Structure
- Nucleosomes coil to form a 30 nm fiber, also known as the solenoid structure.
- This structure further compacts, reducing the DNA length by approximately 40-fold.
- Fully condensed chromosomes achieve a 10,000-fold reduction in length.
- This compaction involves looping of the solenoid structure, anchored to scaffold proteins, followed by additional coiling.
Classification of Chromatin
- Heterochromatin is supercoiled and condensed, with genes within it being inactive.
- Euchromatin is accessible to transcription factors and allows gene transcription.
Role of Chromatin Structure in Regulating Transcription
- Lysines in histones are positively charged, contributing to DNA condensation by interacting with neighboring nucleosomes.
- Acetylation of lysine residues neutralizes the positive charge, promoting looser DNA structure and facilitating transcription.
- Histone acetyltransferases (HATs) are activated by environmental cues to unwind DNA and allow gene expression.
- Histone deacetylases (HDACs) are activated when a gene is not required, leading to DNA condensation and repression of transcription.
Clinical Note
- Abnormal chromatin structure can contribute to disease.
- For example, tumor suppressor genes may be silenced by overly condensed chromatin, potentially leading to cancer.
- Vorinostat, an HDAC inhibitor, is FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL) and has shown potential in treating other solid malignancies.
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Test your knowledge on the structure and function of DNA, including the Central Dogma of Molecular Biology. Questions cover topics such as gene composition, DNA transcription, and the unique characteristics of the double helix. Perfect for students studying molecular biology or genetics.
