Plasticity of mitotic cyclins in promoting the G2–M transition

• DOI: 10.1083/jcb.202409219
• Publication Date: 2025-04-09T13:25:26Z
• Authors: Adrijana Crncec; Ho Wai Lau; Lau Yan Ng; Hoi Tang Ma; Joyce P.Y. Mak; Hon Fung Choi; Tsz Kwan Yeung; Randy Yat Choi Poon

Cyclins and cyclin-dependent kinases (CDKs) orchestrate key events in the cell cycle. However, the uniqueness of individual mitotic cyclins has been a long-standing puzzle. By rapidly removing cyclins in G2 human cells, we found that deficiency of B-type cyclins attenuates mitotic onset and uncouples the G2–M kinase network from mitosis, resulting in sustained activation of PLK1 and cyclin A–CDK1. This culminates in mitotic slippage without completing nuclear envelope breakdown. Remarkably, elevating cyclin A several-fold above its endogenous level is adequate to restore mitosis, allowing cells to survive without B-type cyclins. In contrast, cyclin A is rate-limiting but not essential for G2–M due to compensation by endogenous cyclin B1–CDK2, a non-canonical pair. These findings challenge the traditional indispensable roles of different cyclins and highlight their plasticity. Due to the high malleability of the A- and B-type cyclins, cancer cells may be able to place different weights on different cyclins, while maintaining sufficient CDK activities for successful mitosis.