A (adenine), T (thymine), G (guanine), C (cytosine). A=T (2 H-bonds), G≡C (3 H-bonds). Strands antiparallel: 5'→3' opposite 3'→5'.
Helicase unwinds the double helix; topoisomerase relieves supercoiling ahead of the fork; primase synthesizes RNA primers; DNA polymerase III adds nucleotides 5'→3' onto primers; DNA ligase seals nicks (especially Okazaki fragments on lagging strand).
B. UAA, UAG, UGA — recognized by release factors (no tRNA).
Silent: same amino acid (degenerate code) — no effect. Missense: different amino acid (e.g., sickle-cell: GAG→GUG, Glu→Val). Nonsense: stop codon → truncated protein (e.g., some Duchenne muscular dystrophy). Frameshift: insertion/deletion not multiple of 3 → all downstream codons changed (e.g., Tay-Sachs allele HEXA-1278insTATC).
5' cap (modified guanine — protects from exonucleases, aids ribosome binding); 3' poly-A tail (~200 A's — stability and export); splicing (introns removed, exons joined by spliceosome).
B. Recognize 4–8 bp palindromes (e.g., EcoRI: GAATTC) and produce sticky or blunt ends. Used in cloning to splice DNA from different sources.
(a) mRNA 5'-AUG CGA AAU GGC UAG-3'. (b) AUG=Met (start), CGA=Arg, AAU=Asn, GGC=Gly, UAG=stop. Peptide: Met-Arg-Asn-Gly. (c) Start codon AUG; stop codon UAG.
2²⁵ = 33,554,432 copies (~3.4 × 10⁷). One copy = ~6.5 × 10⁻¹² ng (assuming 1 kb amplicon). Total ≈ 0.22 µg = 220 ng — well above the ~10 ng visibility threshold, so the band will be clearly visible after 25 cycles.
GAG = Glu (charged, hydrophilic). GTG → GUG in mRNA = Val (hydrophobic). Disease: sickle-cell anemia. Hydrophobic patch on β-globin allows polymerization of hemoglobin under low O₂; RBCs deform into rigid sickle shape, blocking capillaries, causing pain crises and hemolysis.
Helicase opens the fork. Leading strand (synthesized continuously toward fork, 5'→3'). Lagging strand (synthesized away from fork in short Okazaki fragments). Each fragment starts with an RNA primer made by primase. DNA pol III extends; pol I removes primers; ligase seals nicks. Both new strands are antiparallel to template.
Initiation: small ribosomal subunit + initiator Met-tRNA recognize 5' cap; scan to start AUG; large subunit joins. Elongation: aminoacyl tRNA enters A site; peptide bond forms (large subunit's peptidyl transferase); ribosome translocates (E exits, P holds chain, A ready for next). Termination: stop codon entering A site recruits release factor; chain hydrolyzed, ribosome dissociates.
Restriction-enzyme cloning: cuts at fixed palindromic sequences; needs compatible sites; mostly used in plasmids/in vitro; insertion not site-specific in genomes. CRISPR-Cas9: programmable via guide RNA (gRNA) — any 20 bp sequence next to a PAM; cuts in vivo at chosen genomic locus; allows precise insertion, deletion, or base editing. CRISPR is faster, cheaper, more versatile but raises ethical issues for germline edits.
Extract DNA, quantify, amplify ~13–20 STR loci by multiplex PCR using fluorescent primers, separate by capillary electrophoresis to read repeat counts, compare allele profile. Each STR locus has many alleles; combined probabilities of matching at all loci can be 1 in 10⁹+, allowing individualization (except identical twins).
(1) Cut the human insulin cDNA and a plasmid with the same restriction enzyme (compatible sticky ends). (2) Ligate insulin gene into plasmid using DNA ligase. (3) Transform competent E. coli (heat-shock or electroporation). (4) Select on agar containing the antibiotic to which the plasmid confers resistance — only transformants grow. (5) Grow large cultures, induce expression, lyse cells, purify insulin chromatographically. Used clinically since 1982 (Humulin), replacing pig/cow insulin.
Risks: off-target edits (unintended cuts) — could disrupt tumour-suppressor genes; mosaicism (some cells edited, others not); unknown long-term effects on heritable genome. Ethical: lack of informed consent (embryos cannot consent and changes pass to offspring); equity (access only to wealthy → "designer babies"); slippery slope to enhancement vs disease prevention. International consensus calls for moratorium on germline editing pending broader societal agreement and demonstrated safety. (Reasoned position acceptable if supported by evidence.)