Biology of cancer lecture 5 cell cycle Karobi Moitra
-
Upload
karobi-moitra-ms-phd -
Category
Documents
-
view
2.200 -
download
3
description
Transcript of Biology of cancer lecture 5 cell cycle Karobi Moitra
![Page 1: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/1.jpg)
Chapter 8:pRb and Control of the
Cell Cycle Clock
Copyright © Garland Science 2007
Karobi Karobi Moitra (Ph.D)Moitra (Ph.D)NCI Frederick , NIHNCI Frederick , NIHCancer Inflammation ProgramCancer Inflammation ProgramHuman Genetics SectionHuman Genetics SectionFrederick MD.Frederick MD.
The Cell Cycle
![Page 2: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/2.jpg)
The cell cycle is a programmedseries of events that enablesa cell to duplicate its contentsand generate 2 daughter cells
![Page 3: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/3.jpg)
Figure 8.3b The Biology of Cancer (© Garland Science 2007)
The Cell Cycle
Resting stage
Gap 1
Synthesis
Gap2
![Page 4: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/4.jpg)
Figure 8.3a The Biology of Cancer (© Garland Science 2007)
The mitotic cell cycle in newt lung cells
Prophase:ChromosomesCondense (blue)
Prophase:Centrosomesbegin to assemble(green)
Metaphase:Chromosomesalign and attachto spindle fibres
Anaphase:Chromosomehalves are pulled apart
Telophase:Chromatidsdecondenseand nuclearmembraneforms
![Page 5: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/5.jpg)
Checkpoint Control
![Page 6: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/6.jpg)
Checkpoint Control
Checkpoint controls in the cell cycle ensure thata new step in the cycle is not undertaken until
the preceding step has been completed.
![Page 7: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/7.jpg)
Figure 8.4 The Biology of Cancer (© Garland Science 2007)
Cell Cycle Checkpoints : Quality Control
![Page 8: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/8.jpg)
What happens if a damaged cell overrides these checkpoints?
![Page 9: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/9.jpg)
Cancer is associated with abnormal cellularproliferation
Cells divide when they should not divide and theylack the normal control systems to shut off unwanted
cell division
![Page 10: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/10.jpg)
Cancer Cells May Lose Checkpoint Controls
Cell death
![Page 11: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/11.jpg)
Figure 8.5a The Biology of Cancer (© Garland Science 2007)
Loss of checkpoint controls result in altered Karyotype
Normal human Rad17 deprived(Rad17 preventsrereplication)
![Page 12: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/12.jpg)
Figure 8.5c The Biology of Cancer (© Garland Science 2007)
Chromosome breaks in cells Lacking ATR (ATR can stall replication to repair breaks)
ATR: ataxia telangiectasia and Rad3 related protein
![Page 13: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/13.jpg)
Figure 8.6 The Biology of Cancer (© Garland Science 2007)
Once a Cell Advances beyond R- restriction point it is committed to advance through the cell cycle and
divide
Go to MRemain in G1Go to G0
![Page 14: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/14.jpg)
Restriction Point :
G1 phase checkpoint in the cell cycle of animal cells
![Page 15: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/15.jpg)
Figure 8.1 The Biology of Cancer (© Garland Science 2007)
The Cell Cycle Clock controls the cell cycle
![Page 16: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/16.jpg)
Table 8.4 The Biology of Cancer (© Garland Science 2007)
![Page 17: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/17.jpg)
Figure 8.8 The Biology of Cancer (© Garland Science 2007)
Each cyclin pairs with a specific cyclin dependentkinase (CDK) to carry out the steps in the cell cycle
![Page 18: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/18.jpg)
Cyclin +cyclin-dependent kinase (CDK)+ CAK = active complex
![Page 19: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/19.jpg)
Figure 8.12 The Biology of Cancer (© Garland Science 2007)
Coordinated cyclin levels during the cellcycle : levels of different cyclins change
at different stages in the cell cycle
![Page 20: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/20.jpg)
Table 8.1 The Biology of Cancer (© Garland Science 2007)
![Page 21: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/21.jpg)
Figure 8.13a The Biology of Cancer (© Garland Science 2007)
p - designation of a tumor suppressor gene
CDK inhibitors block the action of CDK’s at various pointsin the cell cycle
Preventsdamaged cells
to proceed withthe cell cycle and also
causes interchange of CDKsat different stages of the
cell cycle
![Page 22: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/22.jpg)
pRB and cell cycle control
![Page 23: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/23.jpg)
The E2F transcription factor
![Page 24: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/24.jpg)
Transcription factors can turn genes ‘on’
![Page 25: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/25.jpg)
E2F is a transcription factor which can switch on genesthat can cause cell division. Rb can inactivate E2F.
![Page 26: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/26.jpg)
Mutations inactivate pRb, p16 (TSG’s) & the abnormal cell replicates
![Page 27: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/27.jpg)
How can knowledge of the cell cycle can be utilized to develop anticancer drugs?
![Page 28: Biology of cancer lecture 5 cell cycle Karobi Moitra](https://reader035.fdocuments.us/reader035/viewer/2022081422/556af4fad8b42a2a4f8b4706/html5/thumbnails/28.jpg)
The cell cycle is a programmed series of events that enables a cell to duplicate its contents
and generate 2 daughter cells
Checkpoint controls in the cell cycle ensure thata new step in the cycle is not undertaken until
the preceding step has been completed.
Many types of cancer cells have inactivatedone or more of these checkpoint controls to propel
neoplastic growth.