Relative levels of intercellular and intracellular cyclins. (A) Plasticity of mitotic cyclins in human cell lines. During G₂, cyclin B2 is more abundant than cyclin B1 and cyclin A (represented in the diagram by the length of individual bars). The absence of cyclin B1 results in a delay but not inhibition of G₂–M. By contrast, depletion of both cyclin B1 and B2 severely curtailed mitotic entry, leading to cell rounding followed by pre-NEBD slippage. The pre-NEBD G₂ block can be rescued by overexpressing cyclin A (red bars). Similar to cyclin B1, cyclin A is rate-limiting for G₂-M. The G₂-M delay due to cyclin A deficiency can be rescued by overexpression of cyclin B1. Cells were blocked in G₂ in the absence of cyclin A and cyclin B1. (B) Interplay between cyclin A and cyclin B. In the absence of cyclin A, G₂–M is delayed with an accompanied accumulation of cyclin B1–CDK1 and cyclin B1–CDK2 complexes. This delay can be alleviated by overexpression of cyclin B1 (see A). Conversely, the absence of cyclin B1 and B2 hinders proper mitotic entry, leading to pre-NEBD slippage, accompanied by an enrichment of cyclin A-CDK1 and cyclin A-CDK2. Overexpression of cyclin A effectively overcome the pre-NEBD defects.