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 unreplicated 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 unreplicated 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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