Journal Article Review Research Support, Non-U.S. Gov't Epublish
PubMed: 40181639 DOI: 10.1042/BST20253019
Spo11: from topoisomerase VI to meiotic recombination initiator.
Biochem Soc Trans 53(2)
Authors: Jon A Harper, George G B Brown, Matthew J Neale
Affiliations
- Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, U.K.
Abstract
Meiotic recombination is required to break up gene linkage and facilitate faithful chromosome segregation during gamete formation. By inducing DNA double-strand breaks, Spo11, a protein that is conserved in all meiotic organisms, initiates the process of recombination. Here, we chart the evolutionary history of Spo11 and compare the protein to its ancestors. Evolving from the A subunit of archaeal topoisomerase VI (Topo VI), a heterotetrameric type II topoisomerase, Spo11 appears to have evolved alongside meiosis and been present in the last eukaryotic common ancestor. There are many differences between Spo11 and TopVIA, particularly in regulation, despite similarities in structure and mechanism of action. Critical to its function as an inducer of recombination, Spo11 has an apparently amputated activity that, unlike topoisomerases, does not re-seal the DNA breaks it creates. We discuss how and why Spo11 has taken its path down the tree of life, considering its regulation and its roles compared with those of its progenitor Topo VI, in both meiotic and non-meiotic species. We find some commonality between different forms and orthologs of Spo11 in different species and touch upon how recent biochemical advances are beginning to finally unlock the molecular secrets hidden within this fundamental yet enigmatic protein.
MeSH
Recombination, Genetic, Biochemistry, Meiosis