The special chromatin modifications may be recognized as abnormal by cell cycle checkpoints and activate stress response pathway.
The cell cycle consists of four phases, G0/G1, S, G2, and M, which are tightly controlled by cell cycle checkpoints.
Cellular division is carefully monitored by cell cycle checkpoints, which are regulated by cyclins, cyclin-dependent kinases (CDK) and CDK inhibitors (Malumbres and Barbacid, 2001).
These findings are consistent with recent reports [ 39, 40] showing that the progression of early precancerous lesions (in the colon and elsewhere) is curbed by cell cycle checkpoints that are activated by DNA replication "stress".
While some kinases, including PKA, C-TAK, and CAMKII have been shown to phosphorylate S287, they are not regulated by cell cycle checkpoints (Kiyokawa and Ray, 2008, Peng et al., 1998, Duckworth et al., 2002, Hutchins et al., 2003).
The early preinvasive stage was characterized by cell-cycle checkpoint activation triggered by DNA replication stress and dramatic downregulation of basic transmembrane signaling processes that maintain epithelial/stromal homeostasis in the normal mucosa.
Notably, miR-210 facilitates tumor proliferation by activating cell cycle checkpoint and inhibits tumor cell death by decreasing the activity of caspase-8 or lowering the level of reactive oxygen species encouraging tumor cell immortality [ 93 95].
By causing an increase in acetylated histones and other proteins, HDAC inhibitors may disrupt the cell cycle and induce apoptosis of tumour cells by targeting cell cycle checkpoint controls – a G2 check point, which is often defective in tumour cells, and a mitotic spindle check point (Warrener et al, 2003).
