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Vol. 14, No. 1, pp. 81-96, January 1, 2000
Swiss Institute for Experimental Cancer Research, CH-1066
Epalinges/Lausanne, Switzerland
We have examined the cellular function of Sgs1p, a nonessential
yeast DNA helicase, homologs of which are implicated in two highly
debilitating hereditary human diseases (Werner's and Bloom's syndromes). We show that Sgs1p is an integral component of the S-phase
checkpoint response in yeast, which arrests cells due to DNA damage or
blocked fork progression during DNA replication. DNA pol
and Sgs1p
are found in the same epistasis group and act upstream of Rad53p to
signal cell cycle arrest when DNA replication is perturbed. Sgs1p is
tightly regulated through the cell cycle, accumulates in S phase and
colocalizes with Rad53p in S-phase-specific foci, even in the absence
of fork arrest. The association of Rad53p with a chromatin subfraction
is Sgs1p dependent, suggesting an important role for the helicase in
the signal-transducing pathway that monitors replication fork progression.
[Key Words: Sgs1p helicase; DNA replication; checkpoint; DNA damage; Bloom's syndrome; Werner's syndrome]
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