Does the S phase checkpoint account for the flexibility in the timing of DNA replication?
It is not clear whether ongoing DNA replication during an unperturbed S phase triggers the S phase checkpoint, it is detected by a different mechanism or it is not detected at all. Several hypotheses have been drawn in order to accommodate the alleged flexibility in S phase timing. For example, it has been proposed that a licensed but unfired origin, indicative of incomplete replication, could send a signal to block mitosis [21]. Such scenario would require the presence of ongoing forks, since Dbf4-depleted cells show a reductional anaphase despite the fact that they assemble pre-RCs on origins [22,23] (Figure 1). Another possibility is that unreplicated centromeres would activate the spindle checkpoint, as they cannot be bioriented (Figure 1). Although this mechanism of ongoing replication control might operate occasionally, it would be inefficient because of its blindness to replication forks away from centromeres (Figure 1). Another possibility is that a certain threshold in the num
