Let's assume that a cell fails to replicate its DNA during the S Phase of the cell cycle. Let's also assume that the appropriate CDKs are inactive (perhaps due to mutation or lack of cyclin proteins etc.) and the G2-M checkpoint fails.

2 questions:

  1. Will the Spindle Checkpoint fail due to not having duplicated DNA, or can mitosis complete and form aneuploid daughter cells?

  2. More to the point, if mitosis can complete after a cell fails to replicate its DNA (irrespective of the answer to question 1), can the resulting cell (if viable) lead to a neoplasm or cancer?

My thought is no because the odds of having subsequent generations of cells experience similar losses of DNA via mitosis of un-replicated cells would eventually lead to mostly non-viable next-generation cells and the "uncontrolled" division would cease.

  • Though, admittedly, this assumption is dependent on the assumption that the original cell has a heritable issue that "disables" the appropriate checkpoints (vs some random fluke event) allowing the uncontrolled cell line to continue duplicating with un-replicated genomes.

  • I'm also not sure how ultrafine anaphase bridges (see Moreno et al. 2016) can be informative for this question.

I found a paper (Deshpande et al. 2005) that discusses cyclins and cdks in development and cancer, but their paper focuses on the transition form G1 to the S phase and stops short of discussing mitosis of un-replicated cells

Note: this might sound like a homework question, but I'M the one writing the assignment! In fact, it's an exam, and I'm trying to cover my bases for the answers I provide for a different cancer-related question to ensure there are not multiple correct answers.


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