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Questions and Answers
What is the full complement of DNA in a cell called?
What is the full complement of DNA in a cell called?
Which of the following best describes a gene?
Which of the following best describes a gene?
What key structure is formed by the two strands of DNA?
What key structure is formed by the two strands of DNA?
What type of bonds hold the base pairs of DNA together?
What type of bonds hold the base pairs of DNA together?
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What is the primary function of proteins in biological systems?
What is the primary function of proteins in biological systems?
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Which statement best describes the sugar-phosphate backbone of DNA?
Which statement best describes the sugar-phosphate backbone of DNA?
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How many genes are estimated to be in the human genome?
How many genes are estimated to be in the human genome?
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What organism's genome does not contain a nuclear genome?
What organism's genome does not contain a nuclear genome?
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Which bases are complementary in DNA base pairing?
Which bases are complementary in DNA base pairing?
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What holds the sugar-phosphate backbone of DNA together?
What holds the sugar-phosphate backbone of DNA together?
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What type of bond connects the bases to each other in DNA?
What type of bond connects the bases to each other in DNA?
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In which direction are DNA sequences conventionally written?
In which direction are DNA sequences conventionally written?
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What best describes the orientation of the two DNA strands?
What best describes the orientation of the two DNA strands?
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Which of the following forces is the strongest non-covalent interaction holding DNA together?
Which of the following forces is the strongest non-covalent interaction holding DNA together?
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Which component of DNA exposes the edges of the bases to the environment?
Which component of DNA exposes the edges of the bases to the environment?
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Which base pair has the most hydrogen bonds between them?
Which base pair has the most hydrogen bonds between them?
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What substance does methylation of nucleotide bases promote?
What substance does methylation of nucleotide bases promote?
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Which of these modifications promotes DNA relaxation and aids transcription?
Which of these modifications promotes DNA relaxation and aids transcription?
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What type of chromatin is described as supercoiled and condensed?
What type of chromatin is described as supercoiled and condensed?
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What do Histone Acetyl Transferases (HATs) do?
What do Histone Acetyl Transferases (HATs) do?
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Which regions of DNA are consistently in the heterochromatin form?
Which regions of DNA are consistently in the heterochromatin form?
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What is the role of Histone Deacetylases (HDACs)?
What is the role of Histone Deacetylases (HDACs)?
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Which FDA approved drug acts as a HDAC inhibitor?
Which FDA approved drug acts as a HDAC inhibitor?
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How does acetylation affect the interaction between lysines and DNA?
How does acetylation affect the interaction between lysines and DNA?
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What is the primary function of histones in chromatin structure?
What is the primary function of histones in chromatin structure?
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Which of the following correctly describes heterochromatin?
Which of the following correctly describes heterochromatin?
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What is the approximate mass range of histones?
What is the approximate mass range of histones?
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What is a nucleosome composed of?
What is a nucleosome composed of?
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How much does the length of DNA reduce during the initial formation of the 30 nm fiber?
How much does the length of DNA reduce during the initial formation of the 30 nm fiber?
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What is the role of linker DNA in chromatin?
What is the role of linker DNA in chromatin?
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What is the structure formed by coiled nucleosomes called?
What is the structure formed by coiled nucleosomes called?
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Which type of chromatin is associated with active gene expression?
Which type of chromatin is associated with active gene expression?
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What is the primary structure of DNA primarily composed of?
What is the primary structure of DNA primarily composed of?
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Which process is primarily described by the Central Dogma of molecular biology?
Which process is primarily described by the Central Dogma of molecular biology?
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What role do the purine and pyrimidine bases play in the structure of DNA?
What role do the purine and pyrimidine bases play in the structure of DNA?
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What is the significance of the anti-parallel orientation of DNA strands?
What is the significance of the anti-parallel orientation of DNA strands?
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What structural feature of DNA is primarily responsible for its ability to store genetic information?
What structural feature of DNA is primarily responsible for its ability to store genetic information?
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Which types of bonds are crucial for stabilizing the structure of DNA?
Which types of bonds are crucial for stabilizing the structure of DNA?
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What is the consequence of histone modifications in the context of gene expression?
What is the consequence of histone modifications in the context of gene expression?
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Which of the following is true about the composition of the human genome?
Which of the following is true about the composition of the human genome?
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What types of bonds connect the nucleotides within the sugar-phosphate backbone of DNA?
What types of bonds connect the nucleotides within the sugar-phosphate backbone of DNA?
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Which statement accurately describes the hydrogen bonding between base pairs in DNA?
Which statement accurately describes the hydrogen bonding between base pairs in DNA?
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What defines the 5’ and 3’ ends of a DNA strand?
What defines the 5’ and 3’ ends of a DNA strand?
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Which characteristic of DNA strands is essential for their ability to store genetic information?
Which characteristic of DNA strands is essential for their ability to store genetic information?
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What are the areas of a DNA molecule termed that are formed by the sugar-phosphate backbones?
What are the areas of a DNA molecule termed that are formed by the sugar-phosphate backbones?
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What contributes to the stability of a GC-rich region of DNA?
What contributes to the stability of a GC-rich region of DNA?
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Which factor distinguishes the non-covalent forces holding DNA together in terms of strength?
Which factor distinguishes the non-covalent forces holding DNA together in terms of strength?
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What is the correct representation of complementary strands in DNA?
What is the correct representation of complementary strands in DNA?
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What does heterochromatin typically contain?
What does heterochromatin typically contain?
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Which modification promotes DNA relaxation and aids transcription?
Which modification promotes DNA relaxation and aids transcription?
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Which statement describes the role of Histone Deacetylases (HDACs)?
Which statement describes the role of Histone Deacetylases (HDACs)?
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What is the role of environmental cues in chromatin modification?
What is the role of environmental cues in chromatin modification?
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Which regions of DNA are always found in heterochromatin form?
Which regions of DNA are always found in heterochromatin form?
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How does acetylation affect lysine residues on histones?
How does acetylation affect lysine residues on histones?
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What role does Vorinostat play in cancer treatment?
What role does Vorinostat play in cancer treatment?
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What is the effect of methylation on chromatin structure?
What is the effect of methylation on chromatin structure?
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What is the composition of chromatin by weight?
What is the composition of chromatin by weight?
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What type of chromatin is characterized by a highly compact structure with no transcription occurring?
What type of chromatin is characterized by a highly compact structure with no transcription occurring?
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What is the approximate length of DNA wrapped around each nucleosome?
What is the approximate length of DNA wrapped around each nucleosome?
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Which histone protein is associated with linker DNA in the nucleosome structure?
Which histone protein is associated with linker DNA in the nucleosome structure?
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Which structural unit is formed when nucleosomes coil together?
Which structural unit is formed when nucleosomes coil together?
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What is the total approximate reduction in DNA length achieved when chromosomes are fully condensed?
What is the total approximate reduction in DNA length achieved when chromosomes are fully condensed?
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What percentage of basic amino acids do the histones contain, allowing interaction with DNA?
What percentage of basic amino acids do the histones contain, allowing interaction with DNA?
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What is the shape of the nucleosome viewed under an electron microscope?
What is the shape of the nucleosome viewed under an electron microscope?
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What percentage of chromatin is composed of DNA by weight?
What percentage of chromatin is composed of DNA by weight?
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Which histone protein is not part of the nucleosome core but is associated with it?
Which histone protein is not part of the nucleosome core but is associated with it?
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During the coiling of nucleosomes into the 30 nm fiber, by how much is the length of DNA reduced?
During the coiling of nucleosomes into the 30 nm fiber, by how much is the length of DNA reduced?
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What is the primary structural unit of chromatin known as?
What is the primary structural unit of chromatin known as?
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Which statement accurately describes heterochromatin?
Which statement accurately describes heterochromatin?
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How many base pairs are approximately contained within a single nucleosome?
How many base pairs are approximately contained within a single nucleosome?
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What type of structure do nucleosomes form when they coil together?
What type of structure do nucleosomes form when they coil together?
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What is the total reduction in length of DNA achieved in fully condensed chromosomes?
What is the total reduction in length of DNA achieved in fully condensed chromosomes?
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What correctly describes the interaction between the bases of DNA in terms of hydrogen bonds?
What correctly describes the interaction between the bases of DNA in terms of hydrogen bonds?
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Which statement correctly defines the directionality of a DNA strand?
Which statement correctly defines the directionality of a DNA strand?
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Which of the following correctly describes the role of major and minor grooves in DNA?
Which of the following correctly describes the role of major and minor grooves in DNA?
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What is implied by the term 'complementarity' in DNA structure?
What is implied by the term 'complementarity' in DNA structure?
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Which force is the strongest non-covalent interaction supporting the structure of DNA?
Which force is the strongest non-covalent interaction supporting the structure of DNA?
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Which statement best explains the thermodynamic stability of GC-rich DNA regions?
Which statement best explains the thermodynamic stability of GC-rich DNA regions?
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What role do phosphodiester bonds play in DNA's structure?
What role do phosphodiester bonds play in DNA's structure?
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What does the notation 5’-atccggatcgtcc-3’ represent in the context of DNA sequences?
What does the notation 5’-atccggatcgtcc-3’ represent in the context of DNA sequences?
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What characterizes the higher-order structuring of DNA?
What characterizes the higher-order structuring of DNA?
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What is the principal reason for regulating gene expression through histone modification?
What is the principal reason for regulating gene expression through histone modification?
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Which statement correctly describes the organization of chromosomes in the human genome?
Which statement correctly describes the organization of chromosomes in the human genome?
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Which feature of DNA structure allows for a copying mechanism of the genetic material?
Which feature of DNA structure allows for a copying mechanism of the genetic material?
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How do functional RNA molecules like tRNA relate to the concept of genes?
How do functional RNA molecules like tRNA relate to the concept of genes?
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What type of genome structure distinguishes mitochondrial DNA from nuclear DNA?
What type of genome structure distinguishes mitochondrial DNA from nuclear DNA?
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What organizational feature is primarily responsible for DNA's ability to store genetic information?
What organizational feature is primarily responsible for DNA's ability to store genetic information?
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What major milestone in molecular biology was achieved by James Watson and Francis Crick in 1953?
What major milestone in molecular biology was achieved by James Watson and Francis Crick in 1953?
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What is the function of environmental cues in relation to histone acetylation?
What is the function of environmental cues in relation to histone acetylation?
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What structural change can occur when histones are acetylated?
What structural change can occur when histones are acetylated?
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Which statement most accurately describes the difference between euchromatin and heterochromatin?
Which statement most accurately describes the difference between euchromatin and heterochromatin?
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How does methylation generally affect chromatin structure?
How does methylation generally affect chromatin structure?
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Which of the following regions is consistently found in the heterochromatin form?
Which of the following regions is consistently found in the heterochromatin form?
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What is the role of Histone Deacetylases (HDACs) in cellular functions?
What is the role of Histone Deacetylases (HDACs) in cellular functions?
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What is a significant clinical implication of HDAC inhibitors like Vorinostat?
What is a significant clinical implication of HDAC inhibitors like Vorinostat?
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What is the basic structural organization of DNA leading to chromosome formation, in order of compaction?
What is the basic structural organization of DNA leading to chromosome formation, in order of compaction?
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Study Notes
Genome Structure
- Information processing starts with DNA, ultimately producing proteins that determine cell structure and function.
- A gene is a DNA segment directing the synthesis of a specific protein or functional RNA molecule.
- The human genome has approximately 21,000 genes and its complete DNA is called the genome.
DNA Structure & Properties
- DNA is a long, thread-like molecule composed of two strands.
- Each strand consists of deoxyribonucleotides, which are made up of a sugar (deoxyribose), a phosphate group, and one of four nitrogenous bases (adenine, guanine, cytosine, thymine).
- The two strands are anti-parallel and held together by hydrogen bonds between complementary bases: adenine pairs with thymine (A-T) with two hydrogen bonds, and guanine pairs with cytosine (G-C) with three hydrogen bonds.
- The sugar-phosphate backbone is on the exterior of the double helix, while the bases are on the interior.
- The sequence of bases encodes genetic information.
- This structure was discovered by James Watson and Francis Crick in 1953, and it was named the 'double helix'.
- DNA is directional, with a 5' end (free phosphate group) and a 3' end (free hydroxyl group).
- The antiparallel arrangement of the strands refers to the opposite directionality of the 5' and 3' ends of the strands.
Higher Order Structure of Chromosomes
- Human cells have a vast amount of DNA, approximately 3.2 x 10^9 base pairs (bp) distributed across 23 chromosomes.
- Each chromosome is about 3.8 cm long, so a diploid cell contains ~1.8 meters of DNA.
- To fit this DNA inside a cell with a diameter of 10^-6 meters, DNA must be organized and compacted.
Chromatin Structure
- Chromatin is a complex of DNA and proteins, primarily histones, that allows for DNA organization and compaction.
- The complex is essential for cell division and regulates gene expression.
- Heterochromatin is highly compacted, transcriptionally inactive, and associated with gene silencing.
- Euchromatin is less condensed, transcriptionally active, and associated with gene expression.
Histones
- Histones are the major proteins that organize chromatin.
- There are five main types: H1, H2A, H2B, H3, and H4, with a mass of 11-21 kDa.
- They have a high content of positively charged amino acids, allowing them to bind to negatively charged DNA.
The Nucleosome
- The nucleosome is the basic repeating structural unit of chromatin.
- It consists of ~200 bp of DNA wrapped around an octamer of histone proteins (two molecules each of H2A, H2B, H3, and H4).
- H1 histone is associated with the nucleosome 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, known as the '30 nm fiber', which further condenses through looping and anchoring to scaffold proteins.
- This process leads to a 10,000-fold compaction of DNA, allowing it to fit within the nucleus.
Chromatin Structure & Gene Regulation
- Nucleosome structure plays a critical role in gene regulation.
- Acetylation of histone lysine residues neutralizes their positive charge, promoting looser DNA structure and facilitating transcription.
- Deacetylation of histone lysines by histone deacetylases (HDACs) leads to tighter DNA structure and gene silencing.
- These reversible modifications are essential for controlling gene expression.
- Histone acetyltransferases (HATs) activate gene expression by unwinding DNA, while HDACs repress gene expression.
Clinical Significance of Chromatin Modifications
- Aberrant chromatin structure, such as the silencing of tumor suppressor genes, is linked to cancer development.
- HDAC inhibitors, such as Vorinostat, are used to treat certain cancers by promoting the decondensation of chromatin and reactivating silenced genes.
Genome Structure
- Proteins determine the structure and biological activity of cells
- One gene is a length of DNA that directs the synthesis of one protein
- The full complement of DNA is called the genome
- The human genome contains approximately 21,000 genes
- There are also some genes that direct the synthesis of ‘functional’ RNA molecules, like tRNA.
Information Flow
- The central dogma of molecular biology: DNA → RNA → protein
- Francis Crick first proposed the central dogma in 1956
- DNA acts as the storage molecule for genetic information
- RNA is the intermediate carrier
- Proteins perform the functions dictated by the genetic information
Deoxyribonucleic acid (DNA)
- DNA is a long thread-like molecule
- DNA consists of two strands
- There are four different deoxyribonucleotides: adenine (A), guanine (G), thymine (T), and cytosine (C)
DNA Structure
- James Watson and Francis Crick discovered the double helix structure of DNA in 1953
- DNA consists of two polynucleotide strands wound about a common axis in an anti-parallel orientation
- The sugar–phosphate backbone resides on the exterior of the molecule
- The purine and pyrimidine bases reside on the interior of the molecule
- Adenine (A) always pairs with Thymine (T), while Guanine (G) always pairs with Cytosine (C)
DNA Backbone
- Covalent bonds hold the sugar-phosphate backbone together
- 3’ to 5’ phosphodiester bonds connect the nucleotides
Directionality in DNA
- Each strand of DNA has distinct directionality
- The two strands are in anti-parallel orientation
- The 5’ end of a DNA strand has a free hydroxyl or phosphate group at carbon C-5
- The 3’ end of a DNA strand has a free hydroxyl or phosphate group at carbon C-3
Watson-Crick Base Pairing
- Adenine (A) pairs with Thymine (T) via two hydrogen bonds
- Guanine (G) pairs with Cytosine (C) via three hydrogen bonds
Major and Minor Grooves
- The sugar-phosphate backbones create two grooves on the surface of DNA: a major groove and a minor groove
- The edges of the DNA bases are exposed to the surrounding environment in the grooves
Complementarity
- Complementary base pairing means that the two strands of DNA are complementary to each other
- Genetic information is stored in the sequence of bases along a strand of DNA
- By convention, DNA sequences are written from 5’ to 3’
Forces Holding DNA Together
- Covalent bonds are the strongest type of bond, holding DNA together
- Covalent bonds form within nucleotides and the phosphodiester bonds along the backbone
- Non-covalent forces include:
- Base stacking: van der Waals interactions between stacked base-pairs
- Hydrogen bonding: G-C pairing forms three bonds, while A-T pairing forms two bonds
Higher Order Structure of Chromosomes
- Each human cell contains ~3.2 billion base pairs of DNA organised into 23 chromosomes
- The average length of a chromosome is approximately 3.8 cm
- In a diploid cell, there are 46 chromosomes, totalling ~1.8 meters in length
- DNA is complexed with proteins to form chromatin and is organized into compact structures enabling efficient packing within a cell
Chromatin Structure and Organisation
- Chromatin is composed of approximately 50% DNA and 50% protein
- Euchromatin is less compact and allows for transcription
- Heterochromatin is highly compact and prevents transcription
Histones
- Histones are the proteins that organize chromatin
- There are five types of histones: H1, H2A, H2B, H3, and H4
- Histones are rich in positively charged amino acids (lysine and arginine) allowing them to interact with negatively charged DNA
The Nucleosome
- The most basic repeating structural unit of chromatin is the nucleosome
- Each nucleosome consists of:
- ~200 bp of DNA wrapped around a histone core
- 2 molecules each of H2A, H2B, H3, and H4
- 1 molecule of H1 associated with the nucleosome
- The DNA between nucleosomes is called linker DNA
The Nucleosome Core
- The 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
- H1 sits on the outside of the core particle
Higher Levels of Chromosome Structure
- The nucleosomes coil to form a helical or ‘solenoid’ structure of 30 nm diameter known as the ‘30 nm fibre’
- The solenoid loops and these loops are anchored to scaffold proteins, this structure then undergoes further coiling
- This structure enables DNA to be compacted by a factor of ~10,000, allowing it to fit inside the nucleus of a cell
Classification of Chromatin
- Heterochromatin is highly condensed and genes within heterochromatin are not transcribed
- euchromatin is readily accessible to transcription factors and can be transcribed into RNA
Role of Chromatin Structure in Regulating Transcription
- Acetylation of specific histone residues promotes relaxation, allowing accessibility to transcription factors
- Methylation of nucleotide bases promotes compaction, hindering transcription
- Histone Acetyl Transferases (HATs) activate genes by unwinding DNA
- Histone Deacetylases (HDACs) repress gene expression by compacting DNA
Clinical Note
- HDAC inhibitors, such as Vorinostat, have been approved for the treatment of cutaneous T-cell lymphoma (CTCL)
- HDAC inhibitors have also shown efficacy in treating solid malignancies such as colorectal or breast cancer in combination with chemotherapy
Information Flow & Central Dogma
- Proteins are responsible for the structure and function of cells.
- A gene is a segment of DNA that directs the synthesis of a single protein.
- The entire collection of DNA in an organism is called the genome.
- The human genome contains approximately 21,000 genes.
DNA Structure
- DNA is a long, thread-like molecule composed of two strands.
- Each strand consists of four different deoxyribonucleotides.
- The two strands are wound around a common axis in an anti-parallel orientation.
- The sugar-phosphate backbone is located on the exterior of the molecule.
- Purine and Pyrimidine bases are located on the interior.
- The bases pair in a complementary fashion: Adenine (A) pairs with Thymine (T) and Guanine (G) pairs with Cytosine (C).
DNA Backbone
- Covalent bonds hold the sugar-phosphate backbone together.
- These bonds are called 3’ to 5’ phosphodiester bonds.
Directionality of DNA
- Each DNA strand has a distinct directionality, with the two strands being anti-parallel.
- One end of the strand has a free hydroxyl or phosphate group at carbon 5 (5'), known as the 5' end.
- The other end has a free hydroxyl or phosphate group at carbon 3 (3'), known as the 3' end.
Base Pairing in DNA
- The complementary base pairing within DNA serves as the foundation for the storage of genetic information.
- DNA sequences are typically written from 5' to 3'.
Forces Holding DNA Together
-
Covalent Bonds:
- Bonds within nucleotides.
- Phosphodiester bonds along the backbone.
-
Non-Covalent Bonds:
- Base stacking: Van der Waals interactions between stacked base pairs, strongest non-covalent force in the structure.
-
Hydrogen Bonding:
- G-C: 3 hydrogen bonds.
- A-T: 2 hydrogen bonds.
- DNA regions rich in G-C are more thermodynamically stable.
Higher Order Structure of Chromosomes
- Each human cell contains a vast amount of DNA, approximately 3.2 x 10^9 base pairs distributed among 23 chromosomes.
- The average length of a chromosome is 3.8 cm.
- A diploid human cell contains 46 chromosomes, which are more than 1.8 meters long.
- To fit this immense amount of DNA into a small cell, sophisticated packing mechanisms are employed.
Chromatin Structure and Organization
- DNA is complexed with proteins to allow for organized folding into compact structures for cell division.
- This complex is known as chromatin.
- Chromatin consists of approximately 50% DNA and 50% protein by weight.
- Naked DNA is abnormal within the cell.
- Heterochromatin: Highly compact, transcriptionally inactive.
- Euchromatin: More diffuse, allows for transcription.
Histones
- The major proteins involved in chromatin organization are histones.
- There are five types of histones: H1, H2A, H2B, H3, and H4.
- All histones have a high content of positively charged amino acids (Lys and Arg), allowing them to interact with negatively charged DNA.
Nucleosome
- The most fundamental unit of chromatin is the nucleosome.
- Each nucleosome contains:
- ~200 bp of DNA (160-240 bp).
- Two molecules of each histone: H2A, H2B, H3, and H4.
- One molecule of histone H1 is associated with the nucleosome.
- The DNA between nucleosomes is called linker DNA.
Nucleosome Structure
- Histones (excluding H1) form an octamer core particle.
- The nucleosome core is 140 bp of DNA that winds around the octamer in 1.75 turns of a left-handed superhelix.
- Histone H1 sits on the outside of the core particle.
Higher Levels of Chromosome Structure
- Nucleosomes coil to form a 30 nm diameter helical structure known as the 30 nm fibre.
- This structure reduces the length of the DNA by 40-fold.
- In fully condensed chromosomes, a total of 10,000-fold reduction in DNA length is achieved.
- The 30 nm fibre is further looped and anchored to scaffold proteins, undergoing additional coiling.
Chromatin Classification
- Heterochromatin: Highly condensed, transcriptionally inactive region of DNA. Genes within heterochromatin are not expressed. Typically found in regions like telomeres, centromeres, and non-coding regions.
- Euchromatin: More relaxed and accessible to transcription factors. Transcription of genes within euchromatin is possible.
Role of Chromatin Structure in Regulating Transcription
- Lysine residues in histones are positively charged and can interact with negatively charged DNA, leading to DNA condensation.
- Acetylation of lysine residues neutralizes their positive charge, promoting a less condensed DNA structure and making it more accessible for transcription.
- Histone acetyltransferases (HATs) promote DNA unwinding and gene expression, while histone deacetylases (HDACs) promote condensation and decrease transcription.
Clinical Note
- When chromatin is condensed, it can silence genes, including tumor suppressor genes.
- Decondensation of chromatin can activate silenced genes.
- HDAC inhibitors like Vorinostat are used to treat certain cancers, including cutaneous T-cell lymphoma (CTCL).
- Vorinostat can also work in combination with chemotherapy to treat solid cancers.
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Description
Explore the fundamentals of genome structure and DNA properties in this quiz. Delve into how DNA encodes genetic information, the composition of nucleotides, and the significance of base pairing in the double helix. Test your knowledge on the essential concepts that govern molecular biology.