MODULE 4: Molecular Genetics
CHEMISTRY OF NUCLEIC ACIDS, DNA ORGANIZATION & GENOME SEQUENCE CLASSES
1. Chemical Structure
2. Differentiate RNA and DNA based on their structural and chemical charateristics
DNA RNA
Chemical Structure - pentose sugar: deoxyribose - pentose sugar: ribose
- monomeric deoxynucleotide units: - lacks a methyl group -> uracil
> deoxyadenylate, deoxyguanylate, deoxycytidate, thymidylate - ribose comes in fully hydroxylated form
- held together by 3’, 5’ phosphodiester bonds - 2’ –OH
- polymer has a polarity (direction): one end has 5’-hydroxyl - exists as a single strand; does not form analogous double helix
(phosphate terminal), one end has 3’-phosphate (hydroxyl - single strand is capable of folding back on itself (hairpin)
terminal) thus acquiring double-stranded characteristics
- polarity – antiparallel (one strand runs in 5’ to 3’ direction and - G content does not necessarily equal C content
other in 3’-5’ direction) - binds to template strand
- A = T, C = G
- 2 strands are held together by hydrogen bonds bet purine and - “primary structure” – sequence of purine and pyrimidine
pyrimidine nucleotides -> complementary to the template strand of the
- van der Waals & hydrophobic interactions hold together stacked gene from which it was transcribed
/ adjacent base pairs - d/t complementarity, an RNA molecule can bind specifically via
- right-handed; spiral in a clockwise direction base-pairing rules to its template DNA strand
- restrictions: rotation about phosphodiester bond - hybridization – not bind to coding strand of its gene
(anticonfiguration of glycosidic bond)
- genetic information – template strand (copied during RNA
synthesis – transcription) aka noncoding strand
- coding strand – matches sequence of RNA transcript that
encodes protein - forms base pairs with DNA, resulting in heteromeric double
- double helix helix
- can be hydrolyzed by alkali to 2’, 3’ cyclic diesters of the
mononucleotides.
- cannot form 2’, 3’ cyclic diesters. These are compounds that
cannot be formed from alkali-treated DNA because of the absence
of 2’ hydroxyl group
Purine nucleotides Adenine, Guanine Adenine, Guanine
Pyrimidine nucleotides Cytosine, Thymine (methyl group) Cytosine, Uracil
Interneucleotide linkages
DNA Grooves
- found parallel to phosphodiester bonds
- proteins can interact specifically with exposed atoms of nucleotides (via specific hydrophobic and ionic interactions)
- able to recognize and bind to specific nucleotide without disrupting base pairing
▪ Major Groove
▪ Minor Groove
Relaxed and Supercoiled forms
- ends of DNA molecule join to create a closed circle (relaxed / supercoiled form) with no covalently free ends
- does not destroy polarity, but eliminates all free 3’ and 5’ hydroxyl and phosphoryl groups
- supercoils – when a closed circle is twisted around its own axis -> energy requiring process -> torsional stress (supercoils = stress)
- Negative supercoils – twisted in opposite direction -> underwound
- Energy in underwound DNA is stored in the supercoils
- Transition to another form is facilitated by underwinding -> strand separation (prerequisite for DNA replication and transcription)
- Supercoiled DNA – preferred form
- Topoisomerase – enzymes that catalyze topologic changes; relax or insert supercoils using ATP
3. Structural features of DNA as to
3.1. Dominant form -> B DNA
3.2. Differentiate between B and Z atoms
B DNA Z DNA
- stabilized by negative supercoiling generated by
transcription
- transient local conformational change
- zigzag arrangement of backbone molecule = “Z”
- conversion was said to be due to a ‘flipping over’ of base
pairs so that they would have an upside down orientation ,
resulting in syn conformation
- closer phosphate groups
- require alternating purine, pyrimidine sequence
Numbers of strands and its orientation -2 -2
Handedness - right-handed B-DNA form – physiological form of DNA - left handed conformation
double helix
Pitch 3.4nm 4.5nm
AFK
CHEMISTRY OF NUCLEIC ACIDS, DNA ORGANIZATION & GENOME SEQUENCE CLASSES
1. Chemical Structure
2. Differentiate RNA and DNA based on their structural and chemical charateristics
DNA RNA
Chemical Structure - pentose sugar: deoxyribose - pentose sugar: ribose
- monomeric deoxynucleotide units: - lacks a methyl group -> uracil
> deoxyadenylate, deoxyguanylate, deoxycytidate, thymidylate - ribose comes in fully hydroxylated form
- held together by 3’, 5’ phosphodiester bonds - 2’ –OH
- polymer has a polarity (direction): one end has 5’-hydroxyl - exists as a single strand; does not form analogous double helix
(phosphate terminal), one end has 3’-phosphate (hydroxyl - single strand is capable of folding back on itself (hairpin)
terminal) thus acquiring double-stranded characteristics
- polarity – antiparallel (one strand runs in 5’ to 3’ direction and - G content does not necessarily equal C content
other in 3’-5’ direction) - binds to template strand
- A = T, C = G
- 2 strands are held together by hydrogen bonds bet purine and - “primary structure” – sequence of purine and pyrimidine
pyrimidine nucleotides -> complementary to the template strand of the
- van der Waals & hydrophobic interactions hold together stacked gene from which it was transcribed
/ adjacent base pairs - d/t complementarity, an RNA molecule can bind specifically via
- right-handed; spiral in a clockwise direction base-pairing rules to its template DNA strand
- restrictions: rotation about phosphodiester bond - hybridization – not bind to coding strand of its gene
(anticonfiguration of glycosidic bond)
- genetic information – template strand (copied during RNA
synthesis – transcription) aka noncoding strand
- coding strand – matches sequence of RNA transcript that
encodes protein - forms base pairs with DNA, resulting in heteromeric double
- double helix helix
- can be hydrolyzed by alkali to 2’, 3’ cyclic diesters of the
mononucleotides.
- cannot form 2’, 3’ cyclic diesters. These are compounds that
cannot be formed from alkali-treated DNA because of the absence
of 2’ hydroxyl group
Purine nucleotides Adenine, Guanine Adenine, Guanine
Pyrimidine nucleotides Cytosine, Thymine (methyl group) Cytosine, Uracil
Interneucleotide linkages
DNA Grooves
- found parallel to phosphodiester bonds
- proteins can interact specifically with exposed atoms of nucleotides (via specific hydrophobic and ionic interactions)
- able to recognize and bind to specific nucleotide without disrupting base pairing
▪ Major Groove
▪ Minor Groove
Relaxed and Supercoiled forms
- ends of DNA molecule join to create a closed circle (relaxed / supercoiled form) with no covalently free ends
- does not destroy polarity, but eliminates all free 3’ and 5’ hydroxyl and phosphoryl groups
- supercoils – when a closed circle is twisted around its own axis -> energy requiring process -> torsional stress (supercoils = stress)
- Negative supercoils – twisted in opposite direction -> underwound
- Energy in underwound DNA is stored in the supercoils
- Transition to another form is facilitated by underwinding -> strand separation (prerequisite for DNA replication and transcription)
- Supercoiled DNA – preferred form
- Topoisomerase – enzymes that catalyze topologic changes; relax or insert supercoils using ATP
3. Structural features of DNA as to
3.1. Dominant form -> B DNA
3.2. Differentiate between B and Z atoms
B DNA Z DNA
- stabilized by negative supercoiling generated by
transcription
- transient local conformational change
- zigzag arrangement of backbone molecule = “Z”
- conversion was said to be due to a ‘flipping over’ of base
pairs so that they would have an upside down orientation ,
resulting in syn conformation
- closer phosphate groups
- require alternating purine, pyrimidine sequence
Numbers of strands and its orientation -2 -2
Handedness - right-handed B-DNA form – physiological form of DNA - left handed conformation
double helix
Pitch 3.4nm 4.5nm
AFK
