Spo11Protein

Spo11Protein is a conserved eukaryotic protein that initiates meiotic DNA double-strand breaks (DSBs), a crucial first step in homologous recombination that promotes proper chromosome segregation.

Biochemically, Spo11 is related to the A subunit of archaeal topoisomerase VI and catalyzes DSB formation by forming a covalent protein-DNA intermediate via a conserved tyrosine residue. The DSB ends remain covalently attached to Spo11 until nucleolytic processing by the cellular resection machinery.

In yeast and plants, Spo11 works with accessory factors such as Rec102, Rec104, Mer2, Mei4, and Rec114 to localize breaks to specific chromosomal regions and regulate their formation. In vertebrates, SPO11 partners with TOPOVIBL, and there are two paralogs, SPO11-1 and SPO11-2, which together contribute to DSB formation. The breaks are subsequently removed from Spo11 by the action of the MRN complex (MRE11-RAD50-NBS1) and associated nucleases, enabling resection and the generation of 3' single-stranded DNA tails for Rad51 and Dmc1–mediated strand invasion.

Biological significance and regulation are central to Spo11 function. DSB formation is tightly timed and spatially controlled to ensure proper crossover distribution and chromosome alignment during meiosis. Defects in Spo11 activity or subsequent processing can lead to meiotic arrest, infertility, or genome instability.

Evolutionarily, Spo11 is widely conserved across eukaryotes and is derived from topoisomerase VI family enzymes. Its interaction network has diversified across lineages, reflecting adaptations in meiotic control and chromosome biology.