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Running Head: Cell Cycle Progression: A Coordinated Act of Cyclins, Cdks and Checkpoints 1

Cell Cycle Progression: A Coordinated Act of Cyclins, Cdks and Checkpoints

Cell Cycle

Cell division takes place in the eukaryotic cells right from zygote formation till the cell

matures. For the cell division to take place a series of events occur which is called as "cell cycle"

which results in duplication of genome and seperation of complete sets of chromosomes. he cell

cycle includes three phases viz.interphase, mitosis and cytokinesis. !nterphase in turn consists of

# $ap #%, &, and ' $gap '%. Although mitosis and cytokinesis are two different phases, they

happen in (uick succession, that they are almost considered as the same.

G0 phase

his phase commonly refers to (uiescent cells $cells which have stopped dividing%. &enescence is

common for differentiated cells. )eurons for e*ample are permanently in (uiescent state. +*ampes

of cells in semipermanent senescence is liver and kidney cells.epithelial cells for e*ample never

enter senescence state.

Interphase

his is the stage where nutrients re(uired for cell division is accumulated. !nterphase takes

a-out / percentage of the total time of the cell cycle. !nterphase consists of three stages viz. #,

&, and '. !n the & phase replication of 0)A takes place.

G1 phase

he word indicates ap. !t signifies the time period from the end of the 1 phase of the

previous cycle till the start of 0)A transcription. rowth in num-er of orgenelles, supply of proteins

and size happens in this stage.

S phase

& phase starts with 0)A replication. 2ere each chromosome is separated into two sister

chromatids. o avoid mutation, cells replicate as fast as possi-le.

G2 phase

he cells continue to grow after replication. he time period from the & phase to the 1itosis

is called as ap '.

Mitosis

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Cell Cycle Progression: A Coordinated Act of Cyclins, Cdks and Checkpoints 2

he time period of 1itosis is very short. )uclear division which is also called as karyokinesis

takes place in this phase. 1itosis again consists of five phases viz. prophase, metaphase,

anaphase, telophase and cytokinesis.

he cell division starts with the sister chromatids attaching itself to fi-res in the opposite

ends of the cell $1aton, Anthea et al. #3%. )e*t cytokinesis takes place in which nuclei, orgellessuch as mitochondria etc. cytoplasm, and cell mem-ranes are separated in e(ual share in to two

new cells. 1itosis is found to occur e*clusively in eukaryotic cells.

Regulation of Cell Cycle

Cell cycle regulation mechanisms vary from cells to cells. 4egulation mechanisms are

comple* in comple* organisms. 2owever, many of the molecules that control cell cycle is found to

-e common among most of the eukaryotic cells. &uch molecules are cyclindependent kinases

$C05s%, cyclines, etc. Paul 1. )urse, 6eland 2. 2artwell, and 4. imothy 2unt won the '//# )o-el

Prize in 1edicine for the discovery of C05s and cyclins.

Cyclins

Cyclins are proteins that act as catalysts for cyclin dependent kinase $C05% enzymes.

Cyclins together with dependent kinases form maturation promoting factor. he concentration of the

cyclins increases or decreases throughout the cell cycle. 1olecular level signals at specific points

of the cycle determine when cyclins are produced or -roken down. he cyclins e*pressed in the #

phase are called as cyclins 0, whose presence signals the start of the new cell cycle. & Cyclins

such as Cyclin + which is produced during & phase induces 0)A replication. 1 Cyclins i.e. Cyclin 7

induces mitosis in cells.

Cyclin Dependent Kinases(CDKs)

C05s are small proteins that are phosphorylated -y cyclins at serine and threonine

su-strates. Four C05s viz. C05#, ', 8 and 9 are prominently involved in control cell cycle

mechanisms $1argon . 0avid, '//3%. 5inases are inactive for most of the time. nly when they

com-ine with cyclins they -ecome active. All the C05s have AP -inding sites, which are present

as clefts in the protein structure. ;ithout cyclin the loop covers the cleft, there-y inhi-iting the

process.

he cyclinC05 comple*es follow the same activities as the cyclins in the individual phases.

+very cyclinC05 comple* has its own functions. he # cyclinC05 comple*, for e*ample triggers

the cell to go into the &ynthesis phase. his triggers the transcription factors to -e e*pressed and

su-se(uently the synthesis of & cyclins. hese enzymes are responsi-le for 0)A replication. he

C05 comple*es with & cyclin carry out phosphorylation reactions makes sure that the 0)A is

replication only once. Phosphorylation and dephosphorylation -y ;ee# and 1yt# kinases of the

C05s control triggers in C05

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Cell Cycle Progression: A Coordinated Act of Cyclins, Cdks and Checkpoints 3

CDK inhiitory proteins

he C05s are normally found with small inhi-itory proteins and is very important for cell

cycle regulation $&herr and 4o-erts, #%. hree different proteins called as, p'#Cip#, p'35ip#

and p=35ip', are found to form the C05 inhi-itory Proteins.

Maturation !ro"oting #actor

ne of the most wellknown C05cyclin comple*es is the maturation promoting factor or

1PF. 1PF is formed at the end of the ap' phase and triggers the cell>s entry into the 1itosis

phase. 1PF phosphorylates proteins and also activates them which trigger the dissolution of the

nuclear envelope. 1PF concentration is higher in the metaphase of mitosis stage. 7ut the

concentration drops in other stages for the cell to go through other stages. 0uring anaphase, 1PF

helps in degradation of cyclin. he increase

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Cell Cycle Progression: A Coordinated Act of Cyclins, Cdks and Checkpoints 4

4eferences

5arp, erald $'//=%. Cell and 1olecular 7iology: Concepts and +*periments $9th ed.%.

2o-oken, )ew @ersey: @ohn ;iley and &ons. pp. =B.

1aton, Anthea 2opkins, @ean @ohnson, &usan 6a2art, 0avid, Duon ;arner, 0avid, ;right,@ill 0 $#3%. Cells: 7uilding 7locks of 6ife. )ew @ersey: Prentice 2all. pp. 3/B9.

1organ, 0avid . $'//3%. he Cell Cycle: Principles of Control. 6ondon: )ew &cience Press,

#st +d.

&herr, C.@., and 4o-erts, @.1. $#%. C05 inhi-itors: positive and negative regulators of

#phase progression. enes 0ev. #8,#=/#B#=#'.

&tevau*, ., and 0yson, ).@. $'//'%. A revised picture of the +'F transcriptional network

and 47 function. Curr. pin. Cell 7iol. #9, ?9B?#.