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C. Falcone - New tools in deciphering aging and apoptotic pathways
and limited to the S phase. Hydroxyurea (HU)
inhibits DNA replication and causes cell cycle arrest
in S-phase through the inhibition of the ribonucleotide
reductase (RNR), an enzyme that catalyzes
the rate-limiting step in the production of dNTPs.
Cells treated with HU showed low levels of histones
transcripts and synchronized at the beginning of S
phase. In wild type cells, histone transcription peaks
after about 45 min following the release from the HU
block. On the contrary, in the Kllsm4∆1 mutant, histone
transcription starts as soon as HU is removed
suggesting. This result suggests, beside the defect in
mRNA degradation, the existence of an impaired control
of histones genes transcription during cell-cycle.
Following the over-expression of HIR1, histones transcription
is repressed and, although delayed compared
to the wild type, the cyclic expression is restored.
These results suggest that some S phase entry
checkpoints, which repress the transcription of his-
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tone genes before S phase, could be lost in the
Kllsm4∆1 mutant.
It is known that a lag in S phase, caused either by
genetic (i.e. swi6) or chemical means (i.e. hydroxyurea),
enhances silencing.
We observed that the presence of low doses of
hydroxyurea could suppress the premature loss of
viability of the Kllsm4∆1 mutant during chronological
aging, confirming that in this mutant a delay of
entry in S phase recovers some cellular defects.
Selected publications
Mazzoni C, D’Addario I, Falcone C. The C-terminus
of the yeast Lsm4p is required for the association
to P-bodies. FEBS Letters 2007, 581:4836-40.
Mazzoni C, Falcone C. Caspase-dependent apoptosis
in yeast. Biochem Biophys Acta 2008, 1783:1320-7.