SPO11 dimers are sufficient to catalyse DNA double-strand breaks in vitro

First author, Cédric Oger, gives more insight on his latest article published in Nature :

We are interested in SPO11, an enzyme that catalyses the formation of DNA double strand breaks during meiosis. Although such DNA damages are potentially harmful to the cell, the formation of DNA double-strand breaks by SPO11 is programmed at the beginning of meiosis and is conserved across eukaryotes. These breaks are important because they trigger a DNA repair program by homologous recombination that allow the pairing of parental chromosomes, their proper segregation in daughter cells, and promotes genetic diversity by allelic exchanges.

Now, 28 years after the identification of SPO11, we report the first in vitro reconstitution of its DNA cleavage activity in Nature. 

In mouse, SPO11 forms a topoisomerase like complex with the protein TOP6BL and requires a series of additional partners. Surprisingly, we found that in our assay SPO11 alone was sufficient to catalyse DSB. 

Although SPO11 is monomeric in solution, we demonstrate that it assembles dimers to cleave DNA. A key new insight from this work is that dimerization establishes an inherent limitation to catalysis. We therefore propose that, in vivo, SPO11 is recruited by its partners proteins to increase its local concentration, thereby driving dimerization and cleavage. This model explains how the timing and distribution of meiotic double-strand breaks can be regulated to prevent detrimental DNA damage.