Molecular & Cell Biology

S. Rahgozar,PhD

University of Isfahan

Faculty of Science

3. Cell Cycle

3. 2. Cyclins and mitosis

1392-93

Complexes of cyclins and

cyclin-dependent kinases

Mammalian cells

CDC25 Cdk1, cdk2 S, G1, G2

1

Cyclin D1 is rapidly degraded, so its intracellular concentration

rapidly falls if growth factors are removed.

In G1

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.

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.

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.

The events

in M phase

Stages of Mitosis in an animal cell

(Chromosomes

condense)

Mitotic spindles

Break down of

nuclear envelope

Chromosome

decondensation

Regulation of mitosis by Cdk1/cyclinB

Cohensins are members of a class

of “Structural Maintenance of

Chromatin” proteins that play key

roles in the organization of

eukaryotic choromosomes.

Breakdown of

the nuclear

envelope

Breakdown of the Golgi apparatus

fragments into small vesicles

Transport from

the Golgi apparatus

Coat proteins

o Clathrin

o COPI

o COPII

Incorporation of lysosomal proteins into

clathrin-coated vesicles

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

Closed and open mitosis

Progression to Anaphase