SPO11 encodes a meiosis-specific endonuclease that catalyzes the formation of double-strand breaks (DSBs) that are required to initiate meiotic recombination (5). Spo11p forms a dimer; each monomer breaks one strand of the DNA duplex via a transesterification reaction that forms a covalent intermediate between the catalytic tyrosine (Spo11p-Y135) and the 5' end of the DSB (2, 6). Although Spo11p contains the catalytic residue required for DSB formation, multiple other factors are required for the covalent intermediate to be removed and the DSB to be efficiently processed (7, 8, 9, 10). The Spo11p-DSB intermediate can be isolated in a non-null mutant of RAD50 known as rad50S (2). SPO11 is also required for efficient pairing of homologous chromosomes during meiosis I, but SPO11-independent pathways to chromosome pairing exist as well (11, 12, 13, 14).

Consistent with its central role in initiating meiotic recombination, spo11 mutants do not form DSBs, have decreased levels of recombination, and generate inviable spores due to aneuploidy (15, 16, 17, 12). Formation of DSBs with an exogenous factor, such as ionizing radiation, can partially rescue these phenotypes (18). SPO11 expression during early meiosis is regulated by Ume6p (19). Although Spo11p associated with chromatin throughout the genome, not all regions associated with Spo11p are cleaved to become DSBs (20, 21).

Spo11p contains a Toprim domain, which is found in topoisomerases and primases (22. In particular, Spo11p has similarity to the A subunit of topoisomerase 6 (Top6A), an archaeal type II topoisomerase (23). Spo11p is also conserved in S. pombe (rec12+), C. elegans (spo-11), D. melanogaster (mei-86), and H.sapiens (SPO11) (5 and references therein).

Last updated: 2007-07-20