Cell Cycle

Question 1

Cell Cycle- an overview

Answer 1

Involves DNA replication followed by cellular division to yield two daughter cells

Question 2

what does atypical cell cycles lead to?

Answer 2

Uncontrolled cellular proliferation (hallmarks of Cancer)

Question 3

What group of people are cancer incidences high in and low?

Answer 3

High- African American males

Low- American Indian females

Question 4

Proliferation and death throughout organism’s life

Answer 4

In a growing organism, there is more proliferation than death

In an adult organism, cell proliferation and death are in balance

Most cells in an adult organism are cell-cycle arrested

Question 5

Cancer represents an imbalance

Answer 5

Increased rate of proliferation

Decreases rate of cancer cell death

Question 6

Differentiated cells in mature organs- divide or nah?

Answer 6

Examples: nerve cells, striated muscles, cardiomyocytes

DO NOT DIVIDE

Question 7

Cells growing on demand- divide or nah?

Answer 7

Examples: fibroblasts for healing and stems cells for proliferation

DIVIDE

Question 8

Blood Cell precursors- divide or nah? *in adults

Answer 8

Examples: Bone marrow, megakaryocytes, platelets, myeloid cells

DIVIDE

Question 9

G0

Answer 9

The non-dividing phase of the cycle

-resting cells-

Question 10

G0 –> G1

Answer 10

Exposure to mitogenic stimuli such as growth factors or metabolites allows some cells to move onto the cycle

Question 11

G1

Answer 11

Cells are preparing for DNA replication thru growth and metabolism

Question 12

S

Answer 12

DNA replication phase

Question 13

G2

Answer 13

Cells activate enzymes needed for mitosis

Question 14

Interphase

Answer 14

DNA replication takes place (S phase)

Question 15

Prophase & Prometaphase

Answer 15

Chromosomes appear as two thin threads (the chromatids) held together by a centromere

Chromosomes begin to condense

Micro tubules are attached to centrioles on one side and to chromatids on the other

Question 16

Metaphase

Answer 16

The chromatids migrate to the equatorial plane

Question 17

Anaphase/telophase

Answer 17

Separation of 2 sister chromatids and cellular division (cytokinesis)

Question 18

Megakaryocyte- Cell cycle

Answer 18

Skip late anaphase and cytokinesis

Result: polyploidy cell so it can fragment easily

Question 19

Trophoblast- Cell cycle

Answer 19

Skips the late anaphase and cytokinesis phase

result is a polyploidy cell

Question 20

Cancer Cells- cell cycle

Answer 20

Has uneven segregation of chromosomes

Results in uneuploid cells

Question 21

Experimental approach to see how each phase of the cell cycle is regulated?

Answer 21

Isolate cells at each stage and use proteins to see how long each stage lasts

Question 22

How does cyclin fluctuate between interphase and mitosis?

Answer 22

Increases linearly throughout interphase until mid mitosis, and then drops

Picked up again at next interphase

other proteins increase linearly

Question 23

Which cyclins are bound to Cdk2?

Answer 23

Cyclin E or A

Question 24

Which cyclins are bound to Cdk4 or Cdk6

Answer 24

Binds cyclin D

Question 25

Which cyclins are bound to Cdc2

Answer 25

Binds cyclin B

Question 26

Job of CDK

Answer 26

Once bound to cyclin --> phosphorylate so downstream targets which promote a specific cell cycle phase

Question 27

Cyclin complex G2

Answer 27

Cdc2-cyclin B

Question 28

CKI inhibition of Cyclins

Answer 28

Ie: p16, p21 p27 Binds to the cyclin-CDK complex and inactivated it Elevated DKI can inhibit cell cycle progression Elevated cyclins can further promote the cell cycle

Question 29

Cyclin complex G1 and Inhibition

Answer 29

Beginning: CDK 4,6 with cyclin D Inhibited by p16 (CKI and 16 kD) End of G1: CDK2 with cyclin E Inhibited by p21 and p27

Question 30

Cyclin complex S and Inhibition

Answer 30

CDK 2 with Cyclin A Inhibited by p27

Question 31

What are the targets of Cyclin-CDK complexes?

Answer 31

The Rb protein is a tumor suppressor Inhibitory, primary regulated thru transcription Partners with nuclear factor (transcription factor) E2F

Question 32

E2F pathway (normal)

Answer 32

E2F free of Rb is a potent activator of genes involved in DNA synthesis and S phase progression

Question 33

E2F pathway (binded to Rb)

Answer 33

Cdk4-Cyclin D or Cdk6-Cyclin D is capable of phosphorylation get Rb Cdk2-cyclin E further phosphorylate a Rb Phosphorylate do Rb is unable to partner with E2F allowing E2F to bind to S phase gene promotors and activate them

Question 34

How is the E2F/Rb pathway inhibited

Answer 34

By the CKIS- p16, p21, p27

Question 35

Which cancers have D-type cyclins unregulated with a down regulation of p27?

Answer 35

Breast cancer, Colon cancer, Prostate cancer *homogeneity: different levels for each --> some breast cancers will not have high D levels

Question 36

Which cancers have the CKI p16 gene mutated or deleted?

Answer 36

Bladder Deletion- 49% Mutation- 6% Pancreas Deletion- 20% Mutation-27%

Question 37

Other cancers with mutated CKIs

Answer 37

T-ALL Deletion- 57% Mutation- 7% Sporadic Melanoma Deletion- 11% Mutation- 9%