This is consistent with a transient checkpoint-mediated cell-cycle arrest followed by recovery of proliferative capacity.
While the B complex does not appear to be involved in the transient G2-M checkpoint control [ 76], it is required for G2-accumulation checkpoint that is also observed for BRCA1-deficient cells [ 29, 76, 114].
Consequently, the transient arrest followed by checkpoint recovery, especially coupled to decreased apoptosis, will favor survival of TICs.
There is increasing evidence that activation of P38 MAPK by stress stimuli may not necessarily promote cell death but instead also enhance cell survival through activation of a transient G2/M cell cycle checkpoint and successful DNA damage repair.
When we performed a similar experiment with cells synchronized at the metaphase-to-anaphase transition by depletion and reinduction of Cdc20, transient securin destruction and checkpoint-dependent reaccumulation became obvious in cdc14-1, but not cdc15-2, cells.
Cellular effects include inhibition of DNA synthesis and RNA transcription, which leads to the activation of cell cycle checkpoints and transient S-phase arrest followed by a durable G2/M arrest (Shi et al, 1994; Shapiro and Harper, 1999; Gonzalez et al, 2001; Reedijk, 2003; Siddik, 2003).
These employed either transient transfection of GFP tagged checkpoint constructs, or the production of stable cell lines expressing fusion proteins, and in all cases the cell lines also contained the endogenous wild-type checkpoint protein.
Unlike doxorubicin, which causes double-stranded DNA breaks and chronic G2 arrest accompanied by 'templated' CA, Red-Br-nos-mediated DNA damage elicits de novo CA during a transient S/G2 stall, followed by checkpoint abrogation and mitotic entry to form aberrant mitotic figures with supernumerary spindle poles.
As chromosome abnormality caused by erroneous mitosis can lead to severe consequences, mRNA mediated transient modulation of cell division checkpoints or epigenetic state may represent a possible route to improve the quality of in vitro fertilized mammalian embryos without alteration of the embryo genome.
