SMC1α Substitutes for Many Meiotic Functions of SMC1β but Cannot Protect Telomeres from Damage

The cohesin complex is built upon the SMC1/SMC3 heterodimer, and mammalian meiocytes feature two variants of SMC1 named SMC1 alpha and SMC1 beta. It is unclear why these two SMC1 variants have evolved. To determine unique versus redundant functions of SMC1 beta, we asked which of the known functions of SMC1 beta can be fulfilled by SMC1 alpha. Smc1 alpha was expressed under control of the Smc1 beta promoter in either wild-type or SMC1 beta-deficient mice. No effect was seen in the former. However, several major phenotypes of SMC1 beta-deficient sper-matocytes were rescued by SMC1 alpha. We observed extended development before apoptosis and restoration of axial element and synaptonemal complex lengths, chromosome synapsis, sex body formation, processing of DNA double-strand breaks, and formation of MLH1 recombination foci. This supports the concept that the quantity rather than the specific quality of cohesin complexes is decisive for meiotic chromosome architecture. It also suggests plasticity in complex composition, because to replace SMC1 beta in many functions, SMC1 alpha has to more extensively associate with other cohesins. The cells did not complete meiosis but died to the latest at the pachytene-to-diplotene transition. Telomere aberrations known from Smc1 beta(-/-) mice persisted, and DNA damage response and repair proteins accumulated there regardless of expression of SMC1 alpha. Thus, whereas SMC1 alpha can substitute for SMC1 beta in many functions, the protection of telomere integrity requires SMC1 beta.