13.2 DNA Replication and Repair

DNA replication is a crucial process that ensures genetic continuity. It involves unwinding the DNA double helix, synthesizing new strands, and repairing errors. This complex mechanism relies on various enzymes and occurs in a semi-conservative manner.

Understanding DNA replication is key to grasping how genetic information is passed on. It also sheds light on mutations, genetic disorders, and evolution. The process's accuracy and repair mechanisms are vital for maintaining cellular health and preventing diseases like cancer.

DNA Replication Process and Enzymes

Process of DNA replication

• Semiconservative replication produces daughter molecules with one original and one new DNA strand ensuring genetic continuity
• Initiation begins at origin of replication (ori) sites where helicase unwinds DNA double helix creating replication bubble
• Elongation involves DNA primase synthesizing RNA primers followed by DNA polymerase III adding nucleotides to growing strand in 5' to 3' direction
• Okazaki fragments form on lagging strand due to discontinuous synthesis then DNA ligase joins these fragments
• Termination occurs when replication forks meet and telomerase adds telomeres to chromosome ends protecting genetic material

Leading vs lagging strands

• Leading strand synthesized continuously in 5' to 3' direction following replication fork movement requires only one RNA primer
• Lagging strand synthesized discontinuously in 5' to 3' direction opposite to fork movement requires multiple RNA primers forming Okazaki fragments
• Replication fork Y-shaped structure where parental DNA strands separate allowing simultaneous leading and lagging strand synthesis

Mechanisms of DNA repair

• Direct repair reverses UV-induced thymine dimers through photoreactivation (photolyase enzyme)
• Excision repair removes damaged DNA:
  1. Base excision repair (BER) removes damaged bases (uracil DNA glycosylase)
  2. Nucleotide excision repair (NER) removes bulky DNA lesions (UV-induced pyrimidine dimers)
• Mismatch repair corrects errors in base pairing during replication (MutS, MutL proteins)
• Double-strand break repair:
  1. Homologous recombination uses sister chromatid as template (RAD51 protein)
  2. Non-homologous end joining directly ligates broken ends (Ku proteins)

Consequences of replication errors

• Mutations alter genetic information:
  • Point mutations change single nucleotides (sickle cell anemia)
  • Insertions or deletions cause frameshift mutations (cystic fibrosis)
• Chromosomal abnormalities rearrange genetic material:
  • Translocations exchange segments between chromosomes (chronic myeloid leukemia)
  • Inversions reverse DNA segments within chromosomes (hemophilia A)
• Genetic disorders arise from inherited mutations (Huntington's disease)
• Cancer develops through accumulation of mutations in oncogenes and tumor suppressor genes (p53 gene)
• Aging accelerates due to cellular senescence from accumulated DNA damage (Werner syndrome)
• Cell death triggered by excessive DNA damage through apoptosis (radiation exposure)
• Evolution driven by some mutations contributing to genetic diversity and adaptation (antibiotic resistance)