Learning paths

Learning paths

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Learning path

Full curriculum

Full curriculum
  1. Template-directed nucleic-acid synthesis and 5′→3′ polymerization
  2. DNA ligase and sealing of phosphodiester-backbone nicks
  3. Genes, genomes and chromosomes as levels of genetic organization
  4. Semiconservative DNA replication from origins of replication
  5. Replicated chromosomes, sister chromatids, centromeres and kinetochores
  6. DNA damage and mutations as distinct genome changes
  7. Cyclin-CDK control and checkpoints of cell-cycle progression
  8. Heritable variation as the raw material for evolutionary change
  9. DNA sequence substitutions, insertions and deletions
  10. DNA replication fidelity and polymerase proofreading
  11. Post-replicative mismatch repair
  12. Leading- and lagging-strand synthesis at DNA replication forks

Unit content

Semiconservative DNA replication from origins of replication

Before a cell divides, its DNA must be copied so that each daughter cell can inherit a genome. In semiconservative replication, the two strands of a parental DNA duplex separate and each serves as a template for synthesis of a new complementary strand.

The result is two daughter DNA duplexes. Each contains

  • one strand inherited from the parental duplex;
  • one newly synthesized strand.

This is why replication is called semiconservative: each daughter molecule conserves one of the two parental strands.

Replication begins at origins

Replication starts at specific DNA regions called origins of replication. Proteins assemble at an origin and locally open the double helix, creating a replication bubble with two replication forks at its boundaries.

A replication fork is the moving region where parental strands are separated and new DNA is synthesized. Replication commonly proceeds in both directions away from an origin.

Circular bacterial chromosomes can often be copied from a single principal origin, while large eukaryotic chromosomes use many origins so that distant chromosome regions can be copied in parallel.

Complementarity supplies the copying rule

If a parental strand contains

5'-A G C T-3'

its newly synthesized partner must be

3'-T C G A-5'.

No separate sequence blueprint is needed for the second strand: base complementarity lets each old strand specify its new partner.

Opening and copying are coordinated

A helicase is a molecular motor that helps separate the parental DNA strands at a replication fork. DNA polymerases then synthesize complementary DNA on the exposed templates.

The two template strands are antiparallel, while every new DNA strand must be synthesized $5'\rightarrow3'$. That directional constraint creates an asymmetry between the two sides of each fork. The next unit explains how leading- and lagging-strand synthesis solve that problem.

Semiconservative replication therefore combines three ideas: parental strands separate, each becomes a template, and complementary synthesis produces two duplexes that each retain one original strand.