Human Sgo1 Is An Excellent Target For Induction of Apoptosis Of Transformed Cells

Aneuploidy, a frequent form of genomic instability, is a direct result of mis-segregation of sister chromatids during mitosis. Cohesion of sister chromatids in eukaryotes is primarily achieved by the cohesin complex. Since Sgo1 functions to protect centromeric cohesin and since depletion of Sgo1 results in precocious chromosomal segregation and massive mitotic arrest, we reasoned that disruption of Sgo1 functions by delivery of a competitive peptide could interfere with normal cell cycle progression. Treatment of HeLa and A549 cells with a Sgo1 fragment of 22 amino acids (corresponding to a conserved basic region at the C-terminus) linked with a cell-permeable peptide penetratin, but not with penetratin alone, resulted in concentration-dependent suppression of viability. Following 24 h treatment with Sgo1 peptide at a 40 _M final concentration, HeLa cell viability was dramatically reduced. The Sgo1 peptide induced rapid and drastic changes of cell and nuclear morphologies, which were associated with disap...