Biology 335 - Molecular Genetics

Central Dogma - Recombination

The Double Strand Break Model

While the single-strand nick model provides a simple explanation for recombination,
recent work in the yeast Sacchromyces cerevisiae shows that recombination is actually a response to
Double-stranded breaks in the DNA molecule.

The double-strand break model begins with the introduction of a double stranded break in one of the paired homologs (we'll stick with the black and red designations used previously).


Introduction of the double-stranded break results in exonucleolytic degradation of the adjacent strand
in a 5' to 3' direction
resulting in two single-stranded whiskers which can now invade the paired homolog
(again via the action of a RecA like protein).


The invading 3' ends serve as primers for DNA synthesis as shown below


The 3' ends of the newly synthesized strand are then ligated with 5' ends of the degraded red homolog
to form the Double Holiday Junction shown below


These Holiday Junctions are free to migrate as before to generate the heteroduplex regions as shown below


As before, each Holiday Junction can be resolved in two ways...

Resolution I involves breaking and rejoining the two strands that cross between the two homologs
while
Resolution II involves breaking and rejoining the two strands that do not cross between the two homologs

Since there are TWO Holiday Junctions, the exchange of flanking markers depends on how each Holiday Junction is resolved.

If both Holiday Junctions resolve via Resolution I, no exchange of flanking markers is observed as shown below.
Note that the region between the two junctions involves heteroduplex which can be corrected to produce
Gene Conversion.


If Holiday Junction 1 undergoes Resolution I and Holiday Junction 2 undergoes Resolution II,
exchange of flanking markers is observed as shown below.

If Holiday Junction 1 undergoes Resolution II and Holiday Junction 2 undergoes Resolution I,

exchange of flanking markers is again observed as shown below.

Finally, if both Holiday Junctions undergo Resolution II, no exchange of flanking markers is observed.
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Central Dogma - Transcription