Termination of replication forks at the natural termini of the rDNA of 
Saccharomyces cerevisiae is controlled in a sequence-specific and polar mode by 
the interaction of the Fob1p replication terminator protein with the tandem Ter 
sites located in the nontranscribed spacers. Here we show, by both 2D gel 
analyses and chromatin immunoprecipitations (ChIP), that there exists a second 
level of global control mediated by the intra-S-phase checkpoint protein complex 
of Tof1p and Csm3p that protect stalled forks at Ter sites against the activity 
of the Rrm3p helicase ("sweepase"). The sweepase tends to release arrested forks 
presumably by the transient displacement of the Ter-bound Fob1p. Consistent with 
this mechanism, very few replication forks were arrested at the natural 
replication termini in the absence of the two checkpoint proteins. In the 
absence of the Rrm3p helicase, there was a slight enhancement of fork arrest at 
the Ter sites. Simultaneous deletions of the TOF1 (or CSM3), and the RRM3 genes 
restored fork arrest by removing both the fork-releasing and fork-protection 
activities. Other genes such as MRC1, WSS1, and PSY2 that are also involved in 
the MRC1 checkpoint pathway were not involved in this global control. This 
observation suggests that Tof1p-Csm3p function differently from MRC1 and the 
other above-mentioned genes. This mechanism is not restricted to the natural Ter 
sites but was also observed at fork arrest caused by the meeting of a 
replication fork with transcription approaching from the opposite direction.