Central Dogma

Replication

is the process by which a cell duplicates its entire genome before cell division. It is semi-conservative (each new helix has one old strand and one newly synthesized strand) and occurs in the nucleus (eukaryotes) or nucleoid region (prokaryotes).

Helicase

Unzips the DNA double helix by breaking hydrogen bonds.

Topoisomerase (DNA Gyrase)

Relieves the supercoiling tension ahead of the replication fork by cutting and rejoining DNA strands.

PHLE Pharmacology Pearl: Fluoroquinolones (e.g., Ciprofloxacin) inhibit bacterial DNA Gyrase (Topoisomerase II) and Topoisomerase IV. Etoposide inhibits human Topoisomerase II.

Primase

Lays down a short RNA primer to give DNA polymerase a starting point.

DNA Polymerase

Synthesizes the new DNA strand exclusively in the 5' → 3’ direction.

PHLE Pharmacology Pearl: Acyclovir and other antiviral analogs competitively inhibit viral DNA polymerase.

DNA Ligase

Seals the "nicks" between Okazaki fragments on the lagging strand by forming phosphodiester bonds

Transcription (DNA $\rightarrow$ RNA)

_{^{is the process of copying a segment of DNA (a gene) into Messenger RNA (mRNA).}}

• Location: Nucleus (eukaryotes); Cytoplasm (prokaryotes).

• Direction: RNA is synthesized in the 5' → 3’ direction (reading the DNA template strand in the 3' → 5’ direction).

RNA Polymerase I

Synthesizes rRNA (Ribosomal RNA)

RNA Polymerase II

Synthesizes mRNA (Messenger RNA)

RNA Polymerase III

Synthesizes tRNA (Transfer RNA) and 5S rRNA

RNA Polymerases

Board Mnemonic: Rampant, Massive, Tiny (I = rRNA, II = mRNA, III = tRNA).

Post-Transcriptional Modifications (Eukaryotes Only)

In bacteria, transcription and translation happen simultaneously. In humans, the newly made "pre-mRNA" is immature and must be processed before it is allowed to leave the nucleus. This is a massive high-yield topic.

5’ Capping

A 7-methylguanosine cap is added to the $5'$ end. It protects the mRNA from degradation by exonucleases and serves as the binding site for the ribosome during translation.

3’ Polyadenylation (Poly-A Tail)

An enzyme adds roughly 200 Adenine nucleotides to the 3’ end. This protects the tail end of the mRNA and regulates its lifespan in the cytoplasm

RNA Splicing

Introns (Intervening, non-coding sequences) are cut out.

• Exons (Expressed, coding sequences) are spliced together.

• Clinical Note: Mutations in splice sites result in retained introns or skipped exons, leading to dysfunctional proteins (e.g., $\beta$-thalassemia, Marfan syndrome).

Rifampin

a first-line antitubercular drug, binds to the $\beta$-subunit of bacterial DNA-dependent RNA Polymerase, potently inhibiting bacterial transcription. Actinomycin D inhibits both bacterial and eukaryotic transcription.

Translation (RNA $\rightarrow$ Protein)

is the process where ribosomes read the mature mRNA sequence and translate it into a specific sequence of amino acids to form a functional protein.

_{^{Location: Cytoplasm (on free ribosomes) or on the Rough Endoplasmic Reticulum.}}

Pharmacology Pearl: The translation process is the primary target for many antibacterial drugs.

• Buy AT 30: Aminoglycosides and Tetracyclines inhibit the 30S subunit.

• CCEL at 50: Chloramphenicol, Clindamycin, Erythromycin (Macrolides), and Linezolid inhibit the 50S subunit.

mRNA

The instructions, read in sets of three nucleotides called codons.

tRNA

The transport vehicle carrying specific amino acids, matching its anticodon to the mRNA codon.

Ribosomes

• The factory (Prokaryotic = 30S + 50S = 70S; Eukaryotic = 40S + 60S = 80S).

Start Codon

AUG (Methionine)

Stop Codons

UAA, UAG, UGA

Reverse Transcriptase

Certain viruses, specifically Retroviruses (like HIV), carry their genetic material as single-stranded RNA. When they infect a human cell, they use an enzyme called ‘blank’ to synthesize double-stranded DNA from their RNA template. This viral DNA is then permanently integrated into the host's genome.

• Pharmacology Pearl: This is the target for NRTIs (e.g., Zidovudine, Tenofovir) and NNRTIs (e.g., Efavirenz), which are foundational in HIV HAART therapy.

Prions (Protein → Protein Conformation)

Prions are infectious proteins that contain absolutely no nucleic acids (no DNA, no RNA). A misfolded prion protein (PrP^ sc) acts as a template, physically binding to normal proteins (PrP^c) and forcing them to misfold into the disease state. This causes fatal neurodegenerative diseases like Creutzfeldt-Jakob Disease (CJD).