Cell Cycle Flashcards

1
Q

Cell Cycle- an overview

A

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

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2
Q

what does atypical cell cycles lead to?

A

Uncontrolled cellular proliferation (hallmarks of Cancer)

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3
Q

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

A

High- African American males

Low- American Indian females

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4
Q

Proliferation and death throughout organism’s life

A

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

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5
Q

Cancer represents an imbalance

A

Increased rate of proliferation

Decreases rate of cancer cell death

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6
Q

Differentiated cells in mature organs- divide or nah?

A

Examples: nerve cells, striated muscles, cardiomyocytes

DO NOT DIVIDE

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7
Q

Cells growing on demand- divide or nah?

A

Examples: fibroblasts for healing and stems cells for proliferation

DIVIDE

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8
Q

Blood Cell precursors- divide or nah? *in adults

A

Examples: Bone marrow, megakaryocytes, platelets, myeloid cells

DIVIDE

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9
Q

G0

A

The non-dividing phase of the cycle

-resting cells-

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10
Q

G0 –> G1

A

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

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11
Q

G1

A

Cells are preparing for DNA replication thru growth and metabolism

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12
Q

S

A

DNA replication phase

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13
Q

G2

A

Cells activate enzymes needed for mitosis

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14
Q

Interphase

A

DNA replication takes place (S phase)

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15
Q

Prophase & Prometaphase

A

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

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16
Q

Metaphase

A

The chromatids migrate to the equatorial plane

17
Q

Anaphase/telophase

A

Separation of 2 sister chromatids and cellular division (cytokinesis)

18
Q

Megakaryocyte- Cell cycle

A

Skip late anaphase and cytokinesis

Result: polyploidy cell so it can fragment easily

19
Q

Trophoblast- Cell cycle

A

Skips the late anaphase and cytokinesis phase

result is a polyploidy cell

20
Q

Cancer Cells- cell cycle

A

Has uneven segregation of chromosomes

Results in uneuploid cells

21
Q

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

A

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

22
Q

How does cyclin fluctuate between interphase and mitosis?

A

Increases linearly throughout interphase until mid mitosis, and then drops

Picked up again at next interphase

other proteins increase linearly

23
Q

Which cyclins are bound to Cdk2?

A

Cyclin E or A

24
Q

Which cyclins are bound to Cdk4 or Cdk6

A

Binds cyclin D

25
Q

Which cyclins are bound to Cdc2

A

Binds cyclin B

26
Q

Job of CDK

A

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

27
Q

Cyclin complex G2

A

Cdc2-cyclin B

28
Q

CKI inhibition of Cyclins

A

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

29
Q

Cyclin complex G1 and Inhibition

A

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

30
Q

Cyclin complex S and Inhibition

A

CDK 2 with Cyclin A

Inhibited by p27

31
Q

What are the targets of Cyclin-CDK complexes?

A

The Rb protein is a tumor suppressor
Inhibitory, primary regulated thru transcription

Partners with nuclear factor (transcription factor) E2F

32
Q

E2F pathway (normal)

A

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

33
Q

E2F pathway (binded to Rb)

A

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

34
Q

How is the E2F/Rb pathway inhibited

A

By the CKIS- p16, p21, p27

35
Q

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

A

Breast cancer, Colon cancer, Prostate cancer

*homogeneity: different levels for each –> some breast cancers will not have high D levels

36
Q

Which cancers have the CKI p16 gene mutated or deleted?

A

Bladder
Deletion- 49%
Mutation- 6%

Pancreas
Deletion- 20%
Mutation-27%

37
Q

Other cancers with mutated CKIs

A

T-ALL
Deletion- 57%
Mutation- 7%

Sporadic Melanoma
Deletion- 11%
Mutation- 9%