Correct bioriented attachments of microtubules to kinetochores are essential for the faithful segregation of chromosomes during cell division, which is particularly error-prone during meiosis I in mammalian oocytes. Yet, how these errors are rectified remains unclear . To address this , we constructed a simple model of kinetochore-microtubule interaction, which is treated as a Markov process.The model suggests that the balance between attachment and detachment probabilities of kinetochore microtubules is the crucial determinant of the systems dynamics . With the right balance, incorrect attachments are resolved spontaneously into correct bioriented conformations . Our work revealed that a probabilistic URLanization, rather than a sophisticated process of error detection and correction , is responsible for the biorientation of kinetochore-microtubule attachments .
Background: For faithful chromosome segregation during cell division, correct attachments must be established between sister chromosomes and microtubules from opposite spindle poles through kinetochores (chromosome bi-orientation). Incorrect attachments of kinetochore microtubules (kMTs) lead to chromosome mis-segregation and aneuploidy, which is often associated with developmental abnormalities such as Down syndrome and diseases including cancer. The interaction between kinetochores and microtubules is highly dynamic with frequent attachments and detachments. However, it remains unclear how chromosome bi-orientation is achieved with such accuracy in such a dynamic process. Results: To gain new insight into this essential process, we have developed a simple mathematical model of kinetochore-microtubule interactions during cell division in general, i.e. both mitosis and meiosis. Firstly, the model reveals that the balance between attachment and detachment probabilities of kMTs is crucial for correct chromosome bi-orientation . With the right balance, incorrect attachments are resolved spontaneously into correct bi-oriented conformations while an imbalance leads to persistent errors. In addition, the model explains why errors are more commonly found in the first meiotic division (meiosis I) than in mitosis and how a faulty conformation can evade the spindle assembly checkpoint, which may lead to a chromosome loss. Conclusions: The proposed model, despite its simplicity, helps us understand one of the primary causes of chromosomal instability - aberrant kinetochore-microtubule interactions. The model reveals that chromosome bi-orientation is a probabilistic URLanization, rather than a sophisticated process of error detection and correction .
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Correct bioriented attachments of microtubules to kinetochores are essential for the faithful segregation of chromosomes
Background: For faithful chromosome segregation
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which is particularly error-prone during meiosis I in mammalian oocytes. Yet, how these errors are rectified remains unclear . To address this , we constructed a simple
correct attachments must be established between sister chromosomes and microtubules from opposite spindle poles through kinetochores (chromosome bi-orientation). Incorrect attachments of kinetochore microtubules (kMTs) lead to chromosome mis-segregation and aneuploidy, which is often associated with developmental abnormalities such as Down syndrome and diseases including cancer. The interaction between kinetochores and microtubules is highly dynamic with frequent attachments and detachments. However, it remains unclear how chromosome bi-orientation is achieved with such accuracy in such a dynamic process. Results: To gain new insight into this essential process, we have developed a simple mathematical
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interaction, which is treated as a Markov process.The model suggests
interactions during cell division in general, i.e. both mitosis and meiosis. Firstly, the model reveals
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kinetochore microtubules is the crucial determinant of the systems dynamics
kMTs is crucial for correct chromosome bi-orientation
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bioriented conformations . Our work revealed that
bi-oriented conformations while an imbalance leads to persistent errors. In addition, the model explains why errors are more commonly found in the first meiotic division (meiosis I) than in mitosis and how a faulty conformation can evade the spindle assembly checkpoint, which may lead to a chromosome loss. Conclusions: The proposed model, despite its simplicity, helps us understand one of the primary causes of chromosomal instability - aberrant kinetochore-microtubule interactions. The model reveals that chromosome bi-orientation is
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, is responsible for the biorientation of kinetochore-microtubule attachments