Active Transport Can Greatly Enhance Cdc20:Mad2 Formation

International Journal of Molecular Sciences

Bashar Ibrahim¹ 

[1] 1 Al-Qunfudah University College, Umm Al-Qura University, 1109 Makkah Al-Mukarramah, Saudi Arabia

关键词: spindle assembly checkpoint;    chromosome segregation;    systems biology of mitosis;    simulation;    modeling;   

DOI  :  10.3390/ijms151019074

来源: mdpi

【 摘 要 】

To guarantee genomic integrity and viability, the cell must ensure proper distribution of the replicated chromosomes among the two daughter cells in mitosis. The mitotic spindle assembly checkpoint (SAC) is a central regulatory mechanism to achieve this goal. A dysfunction of this checkpoint may lead to aneuploidy and likely contributes to the development of cancer. Kinetochores of unattached or misaligned chromosomes are thought to generate a diffusible “wait-anaphase” signal, which is the basis for downstream events to inhibit the anaphase promoting complex/cyclosome (APC/C). The rate of Cdc20:C-Mad2 complex formation at the kinetochore is a key regulatory factor in the context of APC/C inhibition. Computer simulations of a quantitative SAC model show that the formation of Cdc20:C-Mad2 is too slow for checkpoint maintenance when cytosolic O-Mad2 has to encounter kinetochores by diffusion alone. Here, we show that an active transport of O-Mad2 towards the spindle mid-zone increases the efficiency of Mad2-activation. Our in-silico data indicate that this mechanism can greatly enhance the formation of Cdc20:Mad2 and furthermore gives an explanation on how the “wait-anaphase” signal can dissolve abruptly within a short time. Our results help to understand parts of the SAC mechanism that remain unclear.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.