Chapter 5: DNA Replication, Repair, and Recombination

DNA Replication, Repair, and Recombination begins with the semi-conservative model of DNA replication, detailing how helicases unwind the double helix and DNA polymerases synthesize new complementary strands in the 5' to 3' direction. The chapter describes the asymmetry of the replication fork, highlighting the continuous synthesis of the leading strand and the discontinuous formation of Okazaki fragments on the lagging strand, which are joined by DNA ligase. Key replication machinery such as primase, sliding clamps, and single-strand binding proteins are introduced alongside the role of topoisomerases in relieving torsional strain. The fidelity of DNA replication is maintained by proofreading and mismatch repair systems that recognize and correct errors. The chapter also dives into multiple forms of DNA damage—from spontaneous depurination to UV-induced thymine dimers—and describes cellular repair mechanisms including base excision repair, nucleotide excision repair, and nonhomologous end joining (NHEJ). Homologous recombination is presented as a more accurate mechanism for double-strand break repair, particularly during meiosis, where it also drives genetic diversity through crossing-over. The Holliday junction, strand invasion, and branch migration are covered in detail as steps in this process. Telomerase and telomere maintenance are explained in the context of chromosome end replication, aging, and cancer. The chapter concludes by emphasizing the central importance of genomic integrity to cellular function and how failures in replication or repair can lead to mutagenesis, genomic instability, and disease, including cancer and inherited disorders.