Nucleic Acids: Structure and Function Quiz

Nucleic Acids: Structure and Function

• Nucleic acids are composed of nucleotide building blocks (polynucleotides)
• Two types: ribonucleic acid (RNA) and deoxyribonucleic acid (DNA)
• Each nucleotide consists of a base, a sugar, and one or more phosphate groups
• Bases are nitrogen-containing molecules
• Five different bases: adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U)
• A, C, G, and U are found in RNA
• A, C, G, and T are found in DNA
• Purines: A and G
• Pyrimidines: C, T, and U
• Sugars are monosaccharides (pentoses)
• Ribose is in RNA
• Deoxyribose is in DNA
• Deoxyribose has a H instead of an OH group at the 2' position
• Phosphates can be mono-, di-, or tri-phosphate groups
• Examples include adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP)
• Nucleotides are joined through 3'-5' phosphodiester linkages (covalent bonds)
• Nucleic acids are directional, having 5' and 3' ends
• Sequence of bases is not restricted, storing genetic information
• Bases interact via hydrogen bonds in base pairing
• A pairs with T (in DNA) or U (in RNA)
• G pairs with C
• Hydrogen bonds are individually weak
• Base pairing is specific
• DNA is a double helix
• Two strands coil around the same axis
• Approximately 10 base pairs per turn
• Length of DNA expressed in base pairs (bp)
• 1000 base pairs = 1 kilobase pair (1 kb)
• Human genome has about 3.2 x 10⁹ base pairs
• DNA strands run in opposite directions; antiparallel
• Chemical structure of double-stranded DNA (dsDNA)

DNA Replication

• DNA replication is semi-conservative
• Each strand of DNA serves as a template for a new strand
• Each daughter molecule contains one parental strand and one newly synthesized strand
• DNA replication is bidirectional with multiple origins of replication
• Replication is primed by short stretches of RNA
• Replication is semidiscontinuous
• DNA polymerase is needed for synthesis. It requires a template strand, dNTPs, and a primer with a free 3' end.
• The leading strand is synthesized continuously, while the lagging strand is synthesized discontinuously in short fragments called Okazaki fragments
• RNA primers are needed for lagging strand synthesis
• Primase is DNA-directed RNA polymerase
• DNA polymerase I removes RNA primers and fills the gaps
• DNA ligase seals the nicks
• DNA helicase unwinds the double helix ahead of the replication fork
• Single-stranded DNA-binding proteins keep the two strands separate during replication
• Topoisomerases relieve torsional stress in DNA during replication
• Eukaryotic DNA polymerases have different functions (alpha, beta, delta, epsilon, gamma). Pol alpha inits. DNA synthesis. Pol beta is related to repair. Pol de/ep for lagging/leading strand elongation. Pol is involved in mitochondrial replication

Eukaryotic Cell Cycle

• The cell cycle includes G1, S, G2, and M phases
• S phase includes DNA replication
• G phases are gap phases for cell growth
• M phase includes mitosis (chromosomes segregate)
• Cells that have ceased division are in G0 phase

Eukaryotic DNA Polymerases

• Eukaryotic cells contain various DNA polymerases with specific functions
• Pol α (alpha) initiates DNA synthesis
• Pol β (beta) is related to repair
• Pol δ/ε (delta, epsilon) synthesize the lagging/leading strands

Telomeres

• Telomeres are repetitive DNA stretches at chromosome ends, complexed with proteins
• The telomere sequence in humans is (TTAGGG)_n
• Telomeres shorten with each cell division
• Shortened telomeres prevent cell division
• Cancer and stem cell telomeres do not shorten
• Telomerase is a telomere maintenance enzyme that maintains telomere length

DNA Damage

• Environmental agents (chemicals, radiation) can damage DNA
• Errors in normal cellular processes can cause DNA damage
• Normal chemical changes (e.g., oxidation) can damage DNA
• Mutations are heritable changes in the DNA sequence

Medical Relevance

• Telomeres shorten in normal somatic cells with each division
• Once the telomeres get too short, cells can't divide anymore
• Cancer and stem cells have high telomerase activity which allow continuous division

Related Pharmacology

• DNA synthesis can be inhibited by nucleoside analogs, such as AZT (zodovudine) – a modified sugar component
• AZT is an anti-retroviral drug
• Cytosine arabinoside is anti-cancer drug

Causes of DNA Damage

• Environmental agents like chemicals and radiation (e.g., UV radiation causes adjacent T's to dimerize)
• Errors during normal cellular processes (e.g., incorrect nucleotide incorporation during DNA replication)
• Normal chemical alterations (e.g., oxidation)

Supercoils and Topoisomerases

• As DNA unwinds during replication, supercoils form
• DNA topoisomerases remove supercoils to prevent torsional stress
• Certain antimicrobial and cancer drugs target topoisomerases as a mechanism of action