The simplest explanation for such a tendency would be that K36me1 helps to activate replication origins, but its effect can be counteracted by K36me3.
rG-CSF is able to activate replication of HIV-1 during hematopoietic stem cell mobilization in HIV-1 infected persons [57] and stimulates viral production through binding to CSF3R that is expressed on HIV-1 chronically infected cell lines [58].
In the nucleus, blocks to replication fork progression can activate replication stress response pathways that recruit DNA repair and damage tolerance proteins/enzymes to sites of fork stalling.
Once the population density expands to critical threshold levels, QS systems activate replication programs and the full expression of virulence programs.
Yamasaki et al. showed that OBP-702, p53-expressing and TERT promoter-activated replication-competent Ad induced apoptosis in lung and esophageal carcinoma cells [ 22], but Hasei et al. demonstrated with the same OBP-702 killed osteosarcoma cells through autophagy [ 23].
Consistent with the idea that slowing DNA replication activates the replication checkpoint, we detected HU-dependent Rad53 autophosphorylation by Western blotting, which has been shown to be a direct effect of checkpoint activation in pre-mitotic cells (Pellicioli et al., 1999).
The S phase of the cell cycle is regulated by two checkpoints: one that signals DNA damage (intra-S) and a second that is activated by replication stress (replication checkpoint).
On the other hand, FOXM1 also regulated the expression of Cdc25A phosphatase that was necessary for activating DNA replication; therefore, FOXM1 missing can naturally inhibit mitosis process [ 53].
These experiments further support that Pol κ is required to both prevent incomplete replication intermediates and activate the replication checkpoint in the presence of endogenous or external replication stress.
Whereas the DNA replication checkpoint is activated by replication fork arrest during S phase, the DNA damage checkpoint is activated in G2 phase when damaged DNA is detected.
Replication fork blockage activates the replication checkpoint, which is responsible for slowing of S-phase and cell cycle progression, down-regulation of late origin firing, activation of DNA repair proteins, and stabilization of replication forks (reviewed in Friedel et al. 2009).
