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

First Author  Biswas U Year  2018
Journal  Curr Biol Volume  28
Issue  2 Pages  249-261.e4
PubMed ID  29337080 Mgi Jnum  J:352722
Mgi Id  MGI:6823059 Doi  10.1016/j.cub.2017.12.020
Citation  Biswas U, et al. (2018) SMC1alpha Substitutes for Many Meiotic Functions of SMC1beta but Cannot Protect Telomeres from Damage. Curr Biol 28(2):249-261.e4
abstractText  The cohesin complex is built upon the SMC1/SMC3 heterodimer, and mammalian meiocytes feature two variants of SMC1 named SMC1alpha and SMC1beta. It is unclear why these two SMC1 variants have evolved. To determine unique versus redundant functions of SMC1beta, we asked which of the known functions of SMC1beta can be fulfilled by SMC1alpha. Smc1alpha was expressed under control of the Smc1beta promoter in either wild-type or SMC1beta-deficient mice. No effect was seen in the former. However, several major phenotypes of SMC1beta-deficient spermatocytes were rescued by SMC1alpha. 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 SMC1beta in many functions, SMC1alpha 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 Smc1beta(-/-) mice persisted, and DNA damage response and repair proteins accumulated there regardless of expression of SMC1alpha. Thus, whereas SMC1alpha can substitute for SMC1beta in many functions, the protection of telomere integrity requires SMC1beta.
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