CLINICAL CASES
29
released into the cytoplasm. The chromosomes become aligned on the equato-
rial plate of the cell during
metaphase,
and they move from the equatorial
plate to the poles during
anaphase.
The final step in M phase,
telophase,
is
reformation of the nuclear membrane around the chromosomes followed by
cytokinesis, or formation of two daughter cells. During the G1
phase, the cell
“monitors” itself and its environment. The cell is metabolically active and
undergoes continuous growth, but no DNA synthesis occurs during this phase.
During G1
the cell makes a “decision” either to continue in the cell cycle and
divide or to “withdraw” from the cell cycle and differentiate. The synthesis of
DNA and histones to form two sets of chromosomes occurs during S phase. The
key event of the G2 phase is for the cell to “make sure that its entire DNA has
replicated.” Continued cell growth and the synthesis of cellular macromole-
cules also occur during the G2 phase, preparing for cell division.
Under certain conditions cells can leave G1
and enter into the G0
phase
of
the cell cycle. This phase is not part of the regular cell cycle and represents a
specialized state, which can be temporary or permanent. Entry into the G0 phase
can be triggered by growth factor withdrawal, negative growth factors, or lim-
ited protein synthesis. The cells in G0 are in a
nonproliferative or quiescent
state,
which can vary tremendously in length. Some cells differentiate and never
divide again. Others can resume proliferation to replace lost cells as a result of
injury or cell death. An important point is that cancer cells do not generally have
a G0 phase.
Key regulatory proteins that govern the cell cycle
are the
cyclin-
dependent kinases (CDKs),
which are
serine/threonine protein kinases,
and the
cyclins,
which are regulatory proteins that bind to the CDKs. Proteins
that inhibit the kinase activity (cyclin-dependent kinase inhibitors, or CDIs)
are also present in the cell. The CDKs are regulated by the levels of cyclins
and the CDK/cyclin complex phosphorylates proteins on serine or threonine
residues. The cyclins bind to and activate CDKs via protein—protein interac-
tions. Cyclins act as regulatory subunits controlling activity and specificity
of the CDK activity. These cyclins can themselves be phosphorylated and
dephosphorylated.
Cyclin accumulation and degradation controls normal
cell cycle
activity. For example, the degradation of specific cyclins by prote-
olysis at the metaphase-anaphase transition ends mitosis.
Tetrahydrofolate (THF) is the major source of 1-carbon units
used in
the biosynthesis of many important biological molecules. This
cofactor
is
derived from the
vitamin folic acid
and is a carrier of activated 1-carbon units
at various
oxidation levels (methyl, methylene, formyl, formimino, and
methenyl).
These compounds can be interconverted as required by the cellu-
lar process. The major donor of the 1-carbon unit is
serine
in the following
reaction:
Serine + THF ^ Glycine + N5,N10-methylene-THF
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