Chapter 9: Nucleic Acids Flashcards
Types of nucleic acids
RNA (ribonucleic acid) and DNA (Deoxy ribonucleic acid).
Functions of nucleic acids
- Responsible for storage.
- Transfer of information needed for protein synthesis
DNA
Consists of 2 strands and has primary, secondary, and tertiary structures.
DNA primary structure
- DNA.
- Nucleotides.
- Backbone of DNA.
- Nitrogenous bases.
- Polynucleotides.
- Order of nucleotides.
DNA primary structure: DNA
Formed of deoxyribonucleoside mono phosphate:
1. dGMP
2. dAMP
3. dTMP
4. dCMP
DNA primary structure: nucleotides
Linked by phosphodiester bond between the 5 OH of 1 nucleotide and the 3 OH of the next nucleotide.
DNA primary structure: backbone of DNA
Formed of alternating phosphate and sugar.
DNA primary structure: nitrogenous bases
Projecting to the inside of the 2 strands.
DNA primary structure: polynucleotides
Each polynucleotide strand has 2 terminals:
1. 5’ end: free phosphate attached to the 5’ end of the pentose.
2. 3’ end: free 3’ OH.
DNA primary structure: order of nucleotides
5’ to 3’ direction (direction of synthesis of DNA).
DNA secondary structure
Proposed by Watson and crick in 1953 and won the Nobel prize in 1962.
DNA secondary structure characters
- 2 anti parallel strands forming a right-handed helix.
- Complementary base pairing.
- Stacking of bases.
- Spiral staircase.
- Dimensions.
2 anti parallel strands forming right handed double helix
The 2 strands run anti parallel:
1. Runs in 5 to 3.
2. Runs 3 to 5.
Complementary base pairing
- Adenine and thymine by 2 hydrogen bonds.
- Guanine and Cytosine by 3 hydrogen bonds.
Number of adenine is equal to number of thymine.
Number of guanine is equal to number of cytosine. - The sequence of 1 strand determines the sequence of the other.
- Important for DNA replication in which one strands acts as a template for synthesis of a new strand.
Stacking of bases
The nitrogenous bases are stacked above each other by:
1. Van der waal forces.
2. Hydrophobic interaction.
The stability of the double helix is maintained by:
1. Hydrogen bonds between bases.
2. Van der waals forces.
3. Hydrophobic interactions.
Excessive stacking of bases is balanced by negative charges of the phosphate groups.
Spiral staircase
The double helix of DNA appears like a spiral staircase or twisted ladder.
Dimensions
Each turn: 3.4 nm, 10.4 bp.
2 grooves:
- Major groove: 2.2 nm.
- Minor groove: 1.2 nm.
Many drugs and proteins bind to DNA through these grooves without the need to open the helix (regulation of gene expression).
Desaturation of DNA
Rupture of hydrogen bonds and separation of the 2 DNA strands.
Desaturation of DNA occurs by
Heating
Denaturation of DNA is associated with
Hyperchromicity (increased absorption of UVL).
Renaturation or Renannealing
Rebinding of the 2 strands.
Renaturation occurs by?
Cooling
Renaturation melting point
Temperature that produces loss of 50% of DNA helical structure.
Structural forms of the double helix
- B form: described by Watson and crick.
- A (anyhydride) form.
- Z (zig zag) form.
I
B- DNA type of helix
Right handed
A-DNA
Right handed
Z DNA
Left handed
A DNA shape
Shorter and thicker
Z DNA shape
Longer and thinner
B DNA Major groove
Wide and deep
A DNA major groove
Narrow and deep.
Z DNA
Flat
Variation on major groove
Affect binding of regulatory proteins to DNA which may be important in regulation of gene expression.
B DNA site
Major DNA in the body
A DNA site
Dehydrated DNA
Z DNA
Formed of alternating CG bases.
DNA tertiary structure
- DNA is mainly linear.
- Circular DNA.
Circular DNA is present in?
- Mitochondria.
- Plants (chloroplast).
- Bacteria.
Super coiling of DNA may be:
Positive supercoil: more tight.
Negative supercoil: less tight.
What type of coils are more present under physiological conditions?
Negative supercoils.
Supercoiling of linear DNA
- Toroidal.
- Inter wound coil.
Toroidal
DNA is coiled around a cylinder.
Interwound coil
DNA cross over and under itself.
Supercoiling of circular DNA
- Right handed supercoil.
- Left handed supercoil.
Circular DNA in mitochondria
Eukaryotes have circular DNA in mitochondria.
Plasmid
Circular double stranded DNA present in prokaryotes (bacteria).
Chromatin
DNA in non dividing cells.
Chromatin LM
Not visible
Chromatin EM
Network of fibrils and fibers like beaded thread.
Chromosome
Condensed DNA appears just before cell division (double DNA).
Chromatid
Each chromosome is formed of two identical chromatids.
Each chromatid consists of:
- Single DNA molecule.
- Histone proteins.
- Non histone proteins.
Histone proteins
Basic protein rich in basic amino acids (Arginine, lysine, and histidine).
Charge of Histone proteins
Positively charged (note that DNA is negatively charged).
Histones site
Attached to DNA at the minor groove.
Types of Histone proteins
- H1.
- H2A.
- H2B.
- H3.
- H4.
Histones play a role in:
- DNA Supercoiling.
- Regulation of gene expression.
Nucleosome
Simple unit of chromatin.
Nucleosome is formed of
- Core protein (Histone octamer): 2 copies of (H2A, H2B, H3, and H4.
- One and 3 quarters turns of toroidal DNA: 140 bp.
Nucleosome shape
Nucleosome are linked by linker (spacer) DNA (60 bp) like beads on a string. H1 is attached to linker DNA.
Non Histone proteins
- Attached to major groove.
- Important for regulation of gene expression and help in replication and transcription.
Structure of chromosome
- Formed of 2 identical chromatids connected at the centromere.
- Centromere is rich in A=T base pairs
Telomere
End of chromatid.
Telomere is formed of?
Variable repeats (several kilo bases long) of specific sequence which is (TTAGG).
Packing of DNA
Supercoiling of DNA is important for its packing in the nucleus.
Largest human chromosome is packed in to how many um?
Largest human chromosome is 82mm in length and is packed into 10 um long and 1 um in diameter.
Levels of Supercoiling
Start from packing of DNA around Histone octamer forming Nucleosome reaching the level of a chromosome.
Mitochondrial DNA percentage
0.3%-1% of total cellular DNA.
Mitochondrial DNA shape
Circular double stranded DNA.
MtDNA inheritance
Maternally inherited (provided by ovum).
MtDNA function
Formation of 22 tRNA, 13 protein, and 2 rRNA for oxidative phosphorylation or ETC.
MtDNA defect
Myopathies
MtDNA replication
By DNA polymerase y
Gene
Sequence of nucleotides on DNA coding for a certain character (protein).
Alleles
2 similar genes on the 2 chromosomes coding for the same character.
Genome
Total genetic information (all genes on all cells).
Exons (expressed sequence)
Coding sequence of DNA, unique and never repetitive.
Introns
Non coding sequence, repetitive.
Discontinuity of DNA
DNA is discontinuous, coding sequence (exons) is separated by non coding sequence.
Percentage of exons
2% the rest is non coding.
Introns function
Introns decrease the incidence if mutations and regulate gene expression.
Introns site
Intervening sequence that stay in the nucleus.
Chromosomes
Condensation of DNA (each chromosome contains hundreds to thousands of genes. Each cell has 2 copies of each chromosome (parental and maternal).
Number of chromosomes
Each cell contains 23 pairs of chromosomes:
22 pairs autosomal.
1 pair sec chromosome (XY or XX).
Haploid
Haploid number of chromosomes are present in the gametes (ova and sperms).
Genotype
What is on the inside the gene.
Homozygous
The 2 genes are similar.
Heterozygous
The 2 genes are different.
What is hemizygous?
Phenotype
The physical or biochemical expression of genotype.
Why can the same genotype give more than 1 phenotype?
As many characters as skin, hair color, height, DM) are influenced by many genes and by the environment.
RNA structure
- Formed of ribonucleoside mono phosphate (AMP, GMP, CMP, UMP).
- Nucleotides are connected by phosphodiester bond between 5 OH of 1 nucleotide and 3 OH of the next nucleotide.
- Single stranded.
RNA function
Responsible for protein synthesis.
Types of RNA
- mRNA (messenger RNA).
- rRNA (ribosomal RNA).
- tRNA (transfer RNA).