Homologous recombination

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Homologous recombination Kevin Hiom  Current Biology  Volume 10, Issue 10, Pages R359-R361 (May 2000) DOI: 10.1016/S0960-9822(00)00500-5

Figure 1 (a) Double-strand break repair model for homologous recombination. The double-strand break (DSB) is 5′ to 3′ resected, producing DNA ends with 3′ ssDNA tails. The 3′ ends invade a homologous DNA duplex, forming a DNA crossover or Holliday junction that provides a primer to initiate new DNA synthesis. Branch migration of the Holliday junction extends the region of heteroduplex away from the initial site of crossover. Holliday junctions are resolved by endonucleolytic cleavage of either the crossed strands (green arrows) or non-crossed strands (black arrows) of the junction. Resolution of the two Holliday junctions in different orientations (that is, crossed with non-crossed) will result in the exchange of flanking markers, whereas resolution in the same orientation (crossed with crossed or non-crossed with non-crossed) does not result in exchange of flanking markers. (b) Single-strand annealing model. Single-strand annealing occurs between directly repeated homologous sequences. Resection of a DSB continues until complimentary sequences are revealed. The complimentary sequences are aligned, the non-homologous ends are trimmed and the gaps repaired by DNA synthesis. Recombination of direct repeats by single-strand annealing results in deletion of the intervening DNA and the restoration of a single copy of the repeated sequence. Current Biology 2000 10, R359-R361DOI: (10.1016/S0960-9822(00)00500-5)

Figure 2 .(a) RecA (orange) forms a helical nucleoprotein filament on ssDNA. The ssDNA is stretched to 1.5 times its normal length to facilitate the search for homology. The nucleoprotein filament interacts with naked duplex DNA until homology is found, then strand exchange is initiated, producing a region of heteroduplex DNA. (Adapted with permission from West SC, Ann Rev Biochem 1992, 61:603-640.) (b) The RuvA (light green) and RuvB (dark green) proteins bind to a Holliday junction, opening it out into a planar, cruciform structure. A tetramer of RuvA sits at the crossover point of the junction, while two hexameric RuvB rings sit on opposite arms of the junction with the DNA passing through the centre of each ring. Branch migration is driven by RuvB ‘pumping’ DNA through each ring, in opposite directions, moving the Holliday junction along the DNA. Current Biology 2000 10, R359-R361DOI: (10.1016/S0960-9822(00)00500-5)