DNA Replication and Repair

Before a cell divides it copies its entire genome with remarkable accuracy, and a network of repair systems continually corrects the damage and errors that would otherwise corrupt the inherited sequence.

Definition

DNA replication is the semiconservative copying of the genome in which each parental strand templates a new complementary strand, and DNA repair is the set of enzymatic pathways that detect and correct damage and replication errors.

Scope

This topic covers semiconservative replication and the Meselson-Stahl experiment, the replication fork with its leading and lagging strands and Okazaki fragments, the roles of DNA polymerases, helicase, primase, and ligase, proofreading and the fidelity of synthesis, and the principal repair pathways including mismatch repair, base- and nucleotide-excision repair, and double-strand-break repair. It treats how sequence is copied and preserved; how sequence changes despite these systems is covered under mutation.

Core questions

• How did the Meselson-Stahl experiment demonstrate that replication is semiconservative?
• Why must the two strands at a replication fork be synthesized differently?
• How do proofreading and mismatch repair achieve the genome's very low error rate?
• Which repair pathways handle which kinds of DNA damage?

Key concepts

• Semiconservative replication and the Meselson-Stahl experiment
• Replication fork, leading and lagging strands, Okazaki fragments
• DNA polymerases, helicase, primase, and ligase
• Proofreading and replication fidelity
• Mismatch, excision, and double-strand-break repair

Mechanisms

Helicase unwinds the duplex, primase lays RNA primers, and DNA polymerase extends new strands five-prime to three-prime, continuously on the leading strand and as Okazaki fragments later joined by ligase on the lagging strand; polymerase proofreading and post-replication mismatch repair, together with excision pathways for chemical and ultraviolet damage, keep mutation rates extremely low.

Clinical relevance

Defects in DNA repair cause hereditary disorders and cancer predisposition, such as xeroderma pigmentosum from faulty nucleotide-excision repair and Lynch syndrome from mismatch-repair deficiency, while replication enzymes are the basis of laboratory DNA amplification.

History

Meselson and Stahl confirmed semiconservative replication in 1958 using density-labeled DNA, Kornberg isolated the first DNA polymerase, and the Okazaki fragments discovered in the late 1960s resolved how the lagging strand is made; the repair pathways were progressively mapped through bacterial and human genetics across the following decades.

Key figures

• Matthew Meselson
• Franklin Stahl
• Arthur Kornberg
• Reiji Okazaki

Seminal works

• meselsonStahl1958

Frequently asked questions

What are Okazaki fragments?

They are the short stretches of DNA synthesized discontinuously on the lagging strand because that strand can only be made in the direction opposite to fork movement; an enzyme called DNA ligase later joins them into a continuous strand.

How does the cell keep replication so accurate?

DNA polymerases proofread as they synthesize, removing mismatched nucleotides, and a separate mismatch-repair system scans newly made DNA afterward, together reducing the error rate to roughly one mistake per billion bases.