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39 Cards in this Set

  • Front
  • Back

Cell cycle checkpoints

*arrest the cell cycle


- if previous events have not been completed


- if the environment is unfavorable

G1 checkpoint

*cell cycle checkpoint


(DNA damage checkpoint)


- senses cell size


- physiological state of cell


- environmental conditions

G2 checkpoint

*cell cycle checkpoint


(DNA damage checkpoint)


- ensures DNA is replaced completely/properly

Metaphase checkpoint

*cell cycle checkpoint


- ensures all chromosomes have attached to spindles

DNA damage checkpoint

*cell cycle checkpoints


- arrests cell cycle if DNA is damaged


(ex: G1 checkpoint, G2 checkpoint)

G1 phase

*cell cycle stage


- making a decision whether or not to divide

S-phase

*cell cycle stage


- DNA replication

G2 phase

*cell cycle stage


- making preparations to divide

M-phase

*cell cycle stage


- mitosis and cytokinesis


-- separates sister chromatids


-- divides cell into two daughter cells

Regulations of G1-S phase transition

1) Controlled by molecules (E2F/Rb)


2) Feedback loops

Molecules to control S-phase initiation

*regulation of G1-S transition


- E2F (transcriptional factor)


- Retinoblastoma: Rb (regulatory proteins)

E2F

*regulation of G1-S transition


- Transcriptional factor


- required for transcription of S-phase genes


(G1/S cyclins, S-cyclins, DNA polymerase)


- can transcribe itself




- active when not bound to Rb

S-phase genes

*regulation of G1-S transition


- transcribed by active E2F to enter S-phase


1) G1/S cyclins


2) S-cyclins


3) DNA polymerase


(makes S-cdk)

Retinoblastoma (Rb)

*regulation of G1-S transition


- Regulatory protein


- binds and inhibits E2F


(ex: presence of nitrogens)




- inactive when phosphorylated by G1-Cdk accumulation

Feedback loops

*regulation of G1-S transition


- Sharpen G1/S transition


- regulates itself


- level of one substance influences levels of another in same system

Activation of Cdk/cyclin complex

*regulation of G1-S transition


*Feedback loops


- binding of extracellular signal


- phosphorylates Rb

Incomplete DNA replication

*G2 checkpoint


- blocks entry into mitosis


- blocks cdc25= M-cdk inactive=no mitosis

G2 checkpoint

*cell cycle checkpoint


- ensures that initiation of mitosis cannot occur until DNA replication is complete

Cdc25

*regulates entry into mitosis


- Activates M-cdk


- Promotes entry into mitosis


- Blocked by unreplicated DNA

Hydroxyurea

*regulates entry into mitosis


- inhibits DNA synthesis


- cannot replicate DNA


- cell arrested in S-phase by G2 checkpoint

Caffeine

*regulates entry into mitosis


- blocks G2 checkpoint mechanism


- allows incomplete cells to undergo mitosis/replication

Unattached chromosomes to spindles

*block sister chromatid separation (mitosis)


- done by metaphase checkpoint

Metaphase checkpoint

*cell cycle checkpoint


- spindle assembly checkpoint


- ensures sister-chromatid separation cannot occur until all chromosomes attached to spindle

Unreplicated kinetochore

*regulates chromatid separation in mitosis


- Blocks APC/Cdc20 interaction


-- cannot separate sister chromatids (anaphase)


-- cannot deactivate M-cdk (exit from mitosis)

APC

*regulates chromatid separation in mitosis


- attached to cdc20 (activation)


- blocked by unreplicated kinetochore

Spindle assembly checkpoint mechanism

*regulates sister chromatid separation in mitosis


- activated by drugs


- drugs destabilize MTs


(ex: colchicine)

Colchicine

*regulates sister chromatid separation in mitosis


- drug activated by spindle assembly checkpoint (metaphase checkpoint)


- destabilizes MTs

DNA damage

- blocks cell cycle progression

DNA damage checkpoints

*arrests the cell cycle until damage is repaired


- two types of these in cells


1) G1 checkpoint


2) G2 checkpoint

G1 checkpoint

*DNA damage checkpoint


- prevents entry into S-phase if DNA damaged


- controlled by p53

p53

*controls G1 DNA damage checkpoint


- low in normal cells


- constantly degraded by ubiquitin/protosome


- cannot be degraded when phosphorylated

Active p53

*G1 DNA damage checkpoint


- when phosphorylated


- cannot be degraded


- Transcribes p21 gene


-- blocks S-phase entry

P21

*G1 DNA damage checkpoint


- Cdk inhibitor (CKI)


- transcribed by active phosphorylated p53


- inactivated G1/S-Cdk and S-Cdk


**Blocks entry into S-phase

G2 checkpoint

*DNA damage checkpoint


- prevents mitosis if DNA is damaged


- blocks cdc25 with phosphorylation


- blocks entry into mitosis

Blocks entry into mitosis

*G2 DNA damage checkpoint


- damaged DNA phosphorylates cdc25

G1 phase

*cell cycle phase


- controlled by G1-cdk and G1/S-cdk

p53

*controls DNA damage


*if DNA damaged...


- blocks S-cdk


- blocks G1/S-cdk

Cdc25

*related to M-cdk


- blocked by unreplicated DNA


- blocked by DNA damage

APC

*part of metaphase-anaphase


- blocked by unattached chromosome to spindle