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Summary Pecorino Molecular Biology of Cancer Ch. 5
This is an extensive, English summary of Pecorino's 'Molecular Biology of Cancer' book, Ch. 9 – about the cell cycle.
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Oncology 5HC 5
Cell reproduction is a cyclic process, whereby the cell passes a sequence of stages ending up
in complete cell division. The four stages of the cell cycle are the G1, S, G2 and M-phase. In
short, the G1 and G2 phases are gap phases wherein the cell checks and prepares for the
other phases. The S-phase is for DNA replication/duplication, the M-phase for mitosis or
actual cell division. The overall cell cycle has two main problems to overcome; a perfect
chromosomal duplication and an equal chromosomal segregation. The first problem is
overcome in the S-phase, wherein the double stranded helix is separated by a helicase and
then polymerases duplicate each single strand to render 2 new double stranded helices,
each identical copies of one another. These are kept together by the centromere, which
thus prevents such identical copies, or sister chromatids, from separating already. The
separation occurs in the M-phase, whereby all sister chromatids align in the middle of the
cell, at the equatorial plane (metaphase). Then, a network of microtubules also known as
the mitotic spindle forms which associates and pulls the chromatids apart (anaphase). In the
end, the complete cell cycle takes around 1 day.
5.1
As already slightly discussed, there are four phases of the cell cycle. The G1 phase prepares
for DNA synthesis. For this, the cell is required to grow and accumulate cellular components
to make new DNA – there is a check to ensure if a cell actually wants to copy the DNA. The
S-phase replicates DNA, along with keeping the new copy connected to the original. The G2-
phase prepares for mitosis and the segregation of chromosomes over new daughter cells.
Now again, there is a check: if all DNA is copied successfully, if it is intact and no other
damage – to ensure if a cell actually wants to divide. The M-phase is the mitosis, which has
various sub-phases. In the prophase, the DNA is condensed and the nucleus opened. In the
prometaphase the nucleus is dissolved and the chromosomes move towards the equatorial
plane. In the metaphase, the centromere is removed and the chromosomes are positioned
in the middle of the cell. In the anaphase, the sister chromatids are actually separated.
Then, finally, in the telophase the daughter cells are pinched off through the middle of the
cytoplasm. The state of the cell, as in, in which phase it resides, can be seen through the
microscope; if the chromosomes are condensed it is the M-phase, if not the interphase (G1,
S, G2). At the end of all this, the cell may decide to proceed to the G0 phase, which is a
phase of quiescence and no division occurs.
Transition of one phase to the other is regulated by cyclins and cyclin-dependent kinases
(cdks). They are modulators and function as checkpoints that need to be overcome in order
to proceed the cell cycle. Most cells are not in the process of cell division, but quiescent.
This is an inactive period, the G0-phase, from which cells can only break free if there are
specific growth factors or mitogens signaling to do so. They can enter the G1-phase if they
pass the restriction point – this important threshold, if passed, means the cell is committed
to progress through the cell cycle without growth factors. Rather than mitogens, cyclins and
cdks determining the progression. They cyclically show elevated and regressed
concentration levels in the cell, making them like a switch which pushes the cell over to the
next phase. Different cyclins are elevated at different levels in the cell cycle. The
concentration of cyclins depends on its gene transcription and the regulated protein
degradation. The pairing of cyclins to cdks is highly specific, whereby different cyclin-cdk
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