Why is Homologous Recombination (HR) more frequent at long sequence repeats?

Question

I'm studying plasmids in bacteria (E. coli), and trying to understand the well-cited phenomenon that recombination frequency increases with longer repetitive sequences. I think this also applies to eukaryotes.

In my (potentially misguided) current view, HR can occur between two DNA duplexes either during or after replication (?). As I imagine it, the new DNA duplex will have near identical homology to the template duplex (from which it has just been replicated), meaning that sequence homology is widespread across the entire molecule. This would mean that sufficient homology between sister chromatids can be achieved anywhere (?), negating the trend for 'long sequence repeats'.

So, why is there a focus on long repeats promoting higher recombination frequencies? Is my view on when HR happens misguided?

Answer 1

HR rarely occurs at all in normal somatic cells, because multiple different mechanisms try to prevent this from happening between sister chromosomes during mitosis; the implications of this recombination can be detrimental to the organism. Instead, in eukaryotes, HR normally occurs during Meiosis, in the formation of Gametes, which will recombine anyway. This actually has a beneficial effect because it increases genetic diversity of offspring, thereby promoting evolution.

As for how homologous repeats enhance HR, it is a rather simple mechanism. Basically, you have the two homologous strands side by side, and you have this extensive repeat section in the middle. The thing is, because the repeat section is so long, and because of the fact that it repeats, really any repeated sequence anywhere along that section can cross over with any repeated sequence on the other strand. This increases the availability of HR sites, as well as increases the number of possible outcomes, therefore increasing the probability that HR will occur. Plus, as the number of repeats increases, the number of possible recombinations increases exponentially, making HR on long repeats much more likely than other cases of HR

I hope that satisfactorily answers your question.

Answer 2

I'm not sure what you mean by "repetitive" sequences because homologous regions don't have to be repetitive, but the relation between long homology regions and increased HR efficiency is due to the mechanism. HR in yeast is achieved by strand invasion of single-stranded DNA (perhaps generated by DNA damage or self-induced in the case of meiosis) at another DNA duplex. The longer the homology region, the more complementary base pairing and the stronger the bond. Conversely if the homology region is short then the bonding is not so strong and the single-stranded DNA will probably get displaced by the other strand in the duplex thus reducing HR efficiency. I believe it's similar in E.coli.