DNA Replication & Repair

DNA Replication & Repair

DNA replication is the process of copying the double helix before cell division, ensuring each daughter cell receives an identical genome. It is semi-conservative (Meselson-Stahl experiment) — each new DNA molecule contains one original and one newly synthesized strand.

Key Properties of DNA Replication

  • Semi-conservative: Parent strand serves as template for new strand
  • Bidirectional: Proceeds in both directions from Origin of Replication (ori)
  • Semi-discontinuous: Leading strand synthesized continuously; lagging strand synthesized as Okazaki fragments (100–200 nt in eukaryotes)
  • 5'→3' direction: DNA polymerase only adds nucleotides to 3'-OH end
  • Requires RNA primer: Primase synthesizes short RNA primer (~10 nt) to provide 3'-OH for DNA pol to extend

Key Enzymes in Replication

  • Helicase: Unwinds double helix at replication fork (5'→3' direction); breaks H-bonds between strands
  • Topoisomerase I: Relieves positive supercoiling ahead of fork by nicking and re-sealing one strand
  • Topoisomerase II (Gyrase in bacteria): Relieves supercoiling by cutting both strands. Target: Fluoroquinolones (Ciprofloxacin)
  • SSB Proteins (RPA in eukaryotes): Stabilize single-stranded template
  • Primase: Synthesizes RNA primer. Cannot proofread.
  • DNA Pol III (prokaryotes) / DNA Pol δ, ε (eukaryotes): Main replicative polymerases; 5'→3' synthesis + 3'→5' proofreading (exonuclease)
  • DNA Pol I (prokaryotes): 5'→3' exonuclease removes RNA primers and fills gaps
  • DNA Ligase: Seals nicks between Okazaki fragments (uses NAD+ in bacteria, ATP in eukaryotes)
  • Telomerase: Eukaryotic RNA-dependent DNA polymerase (reverse transcriptase); extends 3' overhang of telomeres; active in germline and cancer cells; absent in somatic cells → telomere shortening → cellular senescence

DNA Repair Mechanisms

  • Direct Repair: O⁶-methylguanine methyltransferase; repairs alkylated guanine directly without strand break
  • Base Excision Repair (BER): Glycosylase removes damaged base → AP site → AP endonuclease → fills gap. Repairs: Oxidized, deaminated, or alkylated bases. AP site (abasic site) = most common DNA lesion.
  • Nucleotide Excision Repair (NER): Removes bulky lesions (UV-induced thymine dimers, crosslinks). Helicase unwinds → 12–25 nt removed → gap filled by DNA pol → ligase. Defective NER → Xeroderma Pigmentosum (UV hypersensitivity, ↑risk of skin cancer). Also Cockayne syndrome, Trichothiodystrophy.
  • Mismatch Repair (MMR): Corrects base-pair mismatches and insertion/deletion loops after replication. Proteins: MLH1, MSH2, MSH6 etc. Defective MMR → Microsatellite Instability (MSI) → Lynch Syndrome (HNPCC) → ↑colon, endometrial, ovarian cancer risk.
  • Double-Strand Break Repair: - Non-Homologous End Joining (NHEJ): Error-prone; predominant in G1 phase; joins ends directly; mediated by Ku proteins + DNA-PK. - Homologous Recombination (HR): Error-free; uses sister chromatid as template; active in S/G2 phase; requires BRCA1, BRCA2, RAD51. BRCA1/2 mutations → ↑breast and ovarian cancer risk.

DNA Damage Causes

  • UV light: Thymine dimers (CPD and 6-4 photoproducts)
  • Ionizing radiation: Double-strand breaks, oxidative damage
  • Alkylating agents (chemotherapy): Add alkyl groups to bases
  • Deamination: Cytosine → Uracil; 5-methylcytosine → Thymine
  • Depurination: Loss of purine bases spontaneously

Quiz - Exam Preparation Strategy

When studying Quiz for your final board exams, it is critical to focus on the core concepts and fundamental formulas. Relying strictly on NCERT textbook solutions and practicing previous year questions (PYQs) is the proven methodology for scoring high marks. Avoid rote memorization and instead focus on the logical application of the theories presented in this chapter.

⚠️ Common Mistakes to Avoid

❓ Frequently Asked Questions

How can I quickly memorize the concepts of Quiz?

The most effective way is to create short, handwritten revision notes and continuously test your knowledge using our interactive Mock Tests. Spaced repetition and active recall are much better than passive reading.

What type of questions are most commonly asked from Quiz?

Board exams tend to favor conceptual application questions and direct formula-based derivations from the NCERT syllabus. Ensure you have solved every single exercise in the official textbook.

Is reading the NCERT book enough for this chapter?

Yes, the NCERT textbook is the absolute gold standard for board exams. However, to improve your speed and accuracy during the actual exam, you must supplement your reading by solving timed mock tests and objective questions.