This document summarizes key aspects of the cell cycle, including cyclins and CDKs, checkpoints, and mitosis. It discusses how cyclin D1 levels fall in response to growth factor removal in G1. It also describes how Cdk2/cyclin E complexes are activated to initiate DNA replication, and how the DNA damage response leads to cell cycle arrest in G1 through p53 and p21. Finally, it provides an overview of the events of mitosis, including chromosome condensation and spindle formation, as well as the role of Cdk1/cyclin B in regulating mitosis.

1. Molecular & Cell Biology
S. Rahgozar,PhD
University of Isfahan
Faculty of Science
3. Cell Cycle
3. 2. Cyclins and mitosis
1392-93

2. Complexes of cyclins and
cyclin-dependent kinases

3. Mammalian cells
CDC25 Cdk1, cdk2 S, G1, G2

4. 1
Cyclin D1 is rapidly degraded, so its intracellular concentration
rapidly falls if growth factors are removed.

5. In G1

6. Cdk2/cyclin E and entry
into S phase
In early G1 , Cdk2/cyclin E
complexes are inhibited by the Cdk
inhibitor p27.
Passage through the restriction
point induces the synthesis of cyclin
E via activation of E2F.
In addition, growth factor signaling
reduces the levels of p27 by
inhibiting its transcription and
translation.
The resulting activation of
Cdk2/cyclin E leads to activation of
the MCM helicase and initiation of
DNA replication.

7. DNA damage
checkpoints
Cell cycle arrest is
mediated by two related
protein kinases, ATM
and ATR, that are
activated in response to
DNA damage.
ATM and ATR
activation also leads to
the activation of DNA
repair and, in some
cases, programmed cell
death.
Phosphorylated Chk2
and Chk1 phosphorylate
and inhibit Cdc25.

8. Role of P53 and p21 in G1 arrest in
mammalian cells
P53 is phophorylated by both ATM and Chk2.
phosphorylation stabilized p53, which is
otherwise rapidly degraded, resulting in a rapid
increase in p53 levels in response to damaged
DNA.
The p53 protein is a transcription factor, and
its increased expression leads to the induction
of the Cip/Kip family Cdk inhibitor p21.
the p21 protein inhibits Cdk2/cyclin E
complexes, leading to cell cycle arrest in G1.

9. The events
in M phase
Stages of Mitosis in an animal cell
(Chromosomes
condense)
Mitotic spindles
Break down of
nuclear envelope
Chromosome
decondensation

10. Regulation of mitosis by Cdk1/cyclinB

11. Cohensins are members of a class
of “Structural Maintenance of
Chromatin” proteins that play key
roles in the organization of
eukaryotic choromosomes.

12. Breakdown of
the nuclear
envelope

13. Breakdown of the Golgi apparatus
fragments into small vesicles

14.  Transport from
the Golgi apparatus
 Coat proteins
o Clathrin
o COPI
o COPII

15. Incorporation of lysosomal proteins into
clathrin-coated vesicles

16. White fish cell at metaphase
Electron micrograph of
microtubules attached to the
kinetochore of a chromosome
The spindle assembly checkpoint
The increased turnover of microtubules in mitosis is
thought to result from phosphorylation of microtubule-
associated proteins, either by Cdk1 or other mitotic
protein kinases such as Aurora and Polo- like kinase

18. Closed and open mitosis

20. Progression to Anaphase