Chap. 19 Problem 1
Passage through the cell cycle is
unidirectional and irreversible due
to the degradation of critical
regulators by proteasome
complexes at specific points
within the cycle (Fig. 19.30).
The APC/C ubiquitin
ligase/proteasome degrades the
protein securin at the beginning
of anaphase, leading to
separation of the sister
chromatids of metaphase
chromosomes. The APC/C
ubiquitin ligase/proteasome
degrades mitotic cyclins at the
end of anaphase, and this
triggers telophase processes and
ultimately entry into G1. Another
ubiquitin ligase/proteasome
complex (the SCF/proteasome) is
responsible for degradation of
the S phase cyclin-CDK inhibitor
at the start of S phase.
Chap. 19 Problem 9
At the START point in the cell cycle,
cells become committed to enter S phase
regardless of whether growth factors are
present or not. In G0 phase, mitogens
stimulate synthesis of G1 cyclin-CDK
(cyclin D-CDK4/6) that in turn
phosphorylates the Rb protein which
controls E2F activity (Fig. 19.15b).
Due to release from Rb control, the E2F transcription factor induces
transcription of genes that promote entry into S phase, including G1/S cyclinCDKs (cyclins E/A-CDK2), S phase cyclin-CDKs, and DNA synthesis enzymes.
a) Cells would no longer require mitogens for exit of G1 if cyclin D were
overexpressed.
b) In the absence of functional Rb, mitogens and cyclin D would not be required
for activation of E2F.
c) p16 (INK4A) inhibits G1/S cyclin-CDKs. Without p16 function, G1/S cyclin
CDKs would promote entry into S phase.
d) In the presence of hyperactive E2F, a number of gene products (including
E2F itself) that promote entry of cells into S phase would be switched on.
(Refer to the first paragraph above).
Chap. 19 Problem 12
When S phase cyclin-CDKs are
activated at the end of G1 due
to the degradation of the S
phase cyclin-CDK inhibitor,
they phosphorylate two
initiation factors and MCM
helicase, which leads to
unwinding of replication origins
and bidirectional DNA synthesis
(Fig. 19.19). The
phosphorylated forms of the
initiation factors cannot rebind
to origins preventing reinitiation of DNA synthesis
during the remainder of the
cell cycle. These factors are
maintained in their
phosphorylated states by S
phase and mitotic cyclin-CDKs
throughout the remainder of
the cell cycle. Only after
these cyclins are degraded at
the end of mitosis can
dephosphorylated initiation
factors assemble again at
replication origins.
Chap. 19 Problem 15
The activation of APC/C ubiquitin ligase by Cdc20 triggers the separation of
sister chromatids during anaphase (Fig. 19.27). Separation is achieved after
APC/C-mediated polyubiquitination and proteasome degradation of the protein
known as securin. Securin normally inhibits a protease (separase), which
cleaves cohesin linkages between sister chromatids when the inhibitor is
degraded. The protein known as Mad2 operates at this checkpoint. Mad2
binds to kinetochores that have not yet bound to microtubules of the mitotic
spindle. Kinetochore binding activates Mad2, and it in turn inhibits the activity
of Cdc20 which controls the activity of the APC/C ubiquitin ligase. This delays
degradation of securin and anaphase until all chromosomes have attached to
the spindle.
Chap. 19 Problem 17
Cell cycle checkpoints are
points where the status of
a cell’s progression through
the cycle is monitored,
and the cell cycle arrested
if a problem is detected.
DNA damage and the
completion of DNA
synthesis are monitored in
G1, S and M phases (Fig.
19.34). Potential problems
with chromosome
segregation and the
assembly of the mitotic
spindle are screened in M
phase. Checkpoint arrests
minimize the transfer of
mutations to the next
generation.