lecture covering details of the cell cycle

7/29/2019 Lecture Covering Details of the Cell Cycle

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Cell Cycle and regulation

Maulik P. Suthar

Cell Biotechnology


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70kg human ~ 1013

cells


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Two processes must alternate during eukaryotic

cell division

Genome must be replicated in S phase

Genome must be halved during M phase

Cell cycle events must behighly regulated in a temporal manner

Genetic and molecular studies in diverse

biological systems have resulted in identification

and characterization of the cell c cle machiner

The Cell Cycle


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G1

Cell CycleG0

6-8 h

DNA, RNA,

Protein

3-4 h

RNA, Protein

1 h

Mitosis, Cytokinesis

S

G2 Cyc DsCDK4,6

Cyc B/ACDK1

Cyc ACDK2

M

Cyc ECDK2

6-12 h RNA, Protein

p53pRb

LaminH1

Abl

The cell cycle engines


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The cell cycle engines

Cyclin Dependent Kinases (CDKs)

CDK

cyclin

substrate

ATP

P

product + ADP


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Cyclin D-CDK4

Cyclin E-CDK2

Cyclin A-CDK2

Cyclin B-CDC2


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Variation in Cell Cycle Cyclins

M G1 G2S M G1

Start

Cell cycle phases

Cyclin-dependent kinases

D E A B(A)cyclins

Cdk4 Cdk2 Cdk1


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CDK activity


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Cyclin D-CDK4

Cyclin E-CDK2

Cyclin A-CDK2

Cyclin B-CDC2

CDKinhibitors


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Cell Cycle Characteristics

Temporally ordered events

Irreversibility

Oscillations

Checkpoints

Positive and negative feedback loops


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pRbpRb

Cell Cycle Regulation

CDK2CE

E2FEnzymes forDNA synthesis

Passage fromG1 to S

DNA damage1. CDK phosphorylation

2. C degradation

3. C & CDK synthesis

4. CDK inhibition

pRb

P

Active p53

p21

pRb


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Positive Feedback Loop


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CDK

cyclin

substrate

ATP

P

product + ADP

p27kip1

CDK

cyclin Inhibited

p27kip1

Model of p27kip1 Function


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Inhibited

p27kip1

CDK

cyclin

Switch

Active

CDK

cyclin p27kip1

P

p27kip1

P

Cell cycle

progression

Switching between Inhibitor and substrate functions


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Review Questions

What are and what happens during the phases of thecell cycle?

Which proteins are involved in the regulation of thecell cycle?

Which cyclins and cyclin-dependent kinases are mostimportant in individual phases of the cell cycle?

What are four mechanisms for regulating cyclin-dependent kinase activity?

What role do p53, p21, and pRb play in the G1 to S

transition?

Questions


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What causes cyclin degradation to turn on and offperiodically?

Why dont rates of synthesis and degradation balance

each other?

There must be some mechanism for switching

irreversibly between phases of net cyclin synthesis and

net cyclin degradation.

Questions


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The Cell CycleThe Cell Cycle

Cells must divide to maintain maximumCells must divide to maintain maximum

efficiency.efficiency.

Mitosis is the process in which somaticMitosis is the process in which somatic

(body) cells divide to form a new cell.(body) cells divide to form a new cell.

Mitosis consists of four phases.Mitosis consists of four phases.

Interphase is the period in between eachInterphase is the period in between eachmitotic cell division.mitotic cell division.


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Interphase

Interphase is made of 3 stages.

The Gap 1 and 2 or G1 and G2 phase is

when cells grow and make RNA, proteins,

and other macromolecules. The S or Synthesis phase is when the cell is

making DNA.


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DNA Replication

During the S phase of the cell cycle, DNA

replicates.

A short section of the DNA uncoils.

New nucleotides bond to the open

sections of the DNA.

The new and old sections of DNAseparate and now there are 2 DNA

strands.


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Interphase

ATP is synthesized.

Damaged parts are repaired.

Wastes are excreted. Proteins are made.

Organelles are formed.

Chromosomes are copied.

Specialized tasks are performed .


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Prophase

Longest phase.

Chromatin coils.

Nucleus disappears.

Centrioles migrate.

Spindle forms.


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Metaphase

Chromatids attach to spindle fibers. Chromatids migrate to equator of spindle.


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Anaphase

Centromere splits.

Chromatids are separated.

Chromatids are now called chromosomes.


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Telophase

Cytoplasm divides. Nucleus reappears.

Chromosomes uncoil.


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Cytokinesis

In the process

called cytokinesis,

the cytoplasm

divides and twoidentical daughter

cells are formed.

lecture covering details of the cell cycle

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