(A) HRT1 is essential. A diploid
hrt1::HIS3/HRT1 strain was transformed with
pRD54-based plasmids (pRS316 CEN, URA3) containing
either yeast HRT1, human HRT1, or human HRT2
under the control of the galactose-inducible GAL1 promoter.
Sporulated diploids were dissected on complete galactose medium,
followed by incubation at 24°C for 5 days. (B,C)
HRT1 is required for both elimination of Sic1 and for S phase.
A myc9 epitope cassette was integrated at HRT1 either
immediately upstream (HRT1–myc9, left) or downstream
(HRT1–stop–myc9, right) of the stop codon. Small
G1 cells were isolated by centrifugal elutriation from
cultures grown in YPD at 25°C and inoculated into fresh medium at
37°C at time 0. In B, mean cell volume (fl), budding index,
formation of mitotic spindles (top panels), and DNA contents
(bottom panels) were assessed at the indicated times. In
C, budding index, Sic1 levels, and Cdc28 levels were
monitored. (D) HRT1 is required for proteolysis of
Sic1. HRT1 cells containing five integrated copies of
GAL–SIC1–HA1 and HRT1–myc9 GAL–SIC1–HA1 (one
copy) cells were grown in YP–raffinose at 25°C (cyc) and arrested
in mitosis with nocodazole (Raff). After shifting the cultures to
32°C, expression from the GAL promoter was induced with
galactose (Gal) and then repressed by transferring the cells to
YP–glucose. Samples were withdrawn at the indicated time points and
assayed for: Swi6 and Sic1-HA1 protein levels (top panels);
calmodulin and SIC1–HA1 mRNA levels (middle panels);
and cellular DNA content (bottom panels). (E)
HRT1 is required for rapid degradation of Cln2. Same as
D, except CLN2–HA3 expression was induced with
galactose at 35°C, and cells were shifted to 37°C upon transfer
to YP–glucose. The band labeled control is an unknown polypeptide
recognized by 12CA5. (F) HRT1 is required for
methionine-dependent repression of MET25 mRNA. Yeast strains
indicated were grown in complete medium containing glucose and lacking
methionine at 25°C and were then shifted to 37°C for 2 hr.
Methionine was added to the medium and samples were withdrawn at the
indicated times. MET25 and CMD1 mRNA levels were
assayed by Northern blotting.