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Homologous recombination by strand invasion and template-directed repair

Homologous recombination (HR) rearranges DNA using extended regions of highly similar sequence. One major use is accurate repair of DNA double-strand breaks by copying information from a homologous DNA molecule.

The defining step is strand invasion: a single-stranded DNA end from the broken molecule pairs with a complementary sequence inside an intact homologous duplex.

From a break to a homologous template

After a double-strand break, enzymes can process the ends to expose single-stranded $3'$ tails. A recombination protein coats one of these tails and promotes a search for matching sequence in another DNA molecule.

When a sufficiently homologous region is found, the single strand pairs with its complement in the intact duplex and displaces the original partner strand. This creates a joint DNA structure.

The invading $3'$ end can then act as a primer for DNA synthesis, using the intact homologous DNA as a template.

Schematically:

broken DNA end
      ↓ end processing
single-stranded 3′ tail
      ↓ homology search
matching duplex found
      ↓ strand invasion
paired 3′ end inside homologous DNA
      ↓ DNA synthesis
missing sequence reconstructed

Why homology can improve accuracy

Unlike direct end joining, HR has access to a long sequence-matched template. If one copy contains a break but another homologous molecule remains intact, missing information can be reconstructed from that second copy.

After DNA synthesis, the recombination intermediates must be rearranged and resolved so that continuous DNA molecules are restored.

Depending on how the joint molecules are resolved, the process can produce either

  • a noncrossover outcome, in which flanking DNA remains associated with its original molecule;
  • a crossover outcome, in which DNA segments on opposite sides of the recombination region are exchanged between the participating molecules.

The molecular mechanism of homology search and strand exchange is shared across contexts. Cells use it for DNA repair, and meiotic cells later exploit related homologous-recombination machinery to exchange chromosome segments deliberately.

Homologous recombination is therefore both a genome-maintenance mechanism and a molecular foundation for genetic recombination.