This behavior is similar to weak checkpoints seen in Drosophila cleavage cycles, although one key difference is that there is no evidence of centrosome inactivation in Hydractinia.
Alternatively, establishment of good biomarkers for detection of weak checkpoint signaling, such as antibodies to post-translational modifications that determine strong vs weak signaling, may facilitate this.
The Mre11/Tel1 complex contributes to a weak checkpoint pathway, termed the TM pathway (Usui et al, 2001).
Our data support a two-stage model for the DDR at uncapped telomeres; Pif1 and Exo1 resect telomeric DNA <5 kb from the chromosome end, stimulating weak checkpoint activation; resection is extended >5 kb by Exo1 and full checkpoint activation occurs.
Defects in the checkpoint were observed only at low doses of taxol, possibly suggesting that Aurora B activity is required primarily to amplify weak checkpoint signals, for example when the occasional bi-oriented kinetochore briefly releases its microtubules due to defective tension.
Actually, there are evidences that a weak mitotic checkpoint correlates with an increase in aneuploid cells.
We propose that close to the chromosome end (<5 kb) both Pif1- and Exo1-dependent activities generate ssDNA, causing weak initial checkpoint activation.
For example, DLD-1 colon cancer cells, which have a relatively weak spindle checkpoint and are slippage-prone, only transiently phosphorylate Bcl-xL/Mcl-1 in response to Taxol, and after slippage, survive or die in subsequent interphase.
The rapidly dividing early embryo has relatively weak cell-cycle checkpoints, which allow continued cycling even when essential processes, such as DNA replication, are defective (Brauchle et al., 2003; Budirahardja and Gönczy, 2009; Encalada et al., 2000).
Weak inaccuracies in mitotic checkpoints are believed to be responsible for aneuploidy and genetic instability, which are inherent to cancer cells and drive tumor progression.
