Bio 305 Cell Cycle

G1 -> S phase

checks size, enough nutrients, genome ready to be duplicated, repaired

start/restriction point

helicases are loaded onto origins of replication

G2 -> M

checks if chromosomes are ready to be separated

cyclin-CDKs

control cell cycle and integrate signals from pathways

Cyclins

proteins that accumulate during G1 and G2 to activate CDKs by binding, controls movement between cell cycle stages

Ubiquitination

mark for degradation, controls cyclins, and recognized by proteosome

Cyclin kinase inhibitor

Bind to CDK to inhibit its activity, p16 (cyclin) and p27 (ATP)

Order of cyclin

DEAB

Order of CDK

4221

cyclin-CDK regulation

phosphorylation and direct (steric/allosteric) binding to increase activity

E3 ligases

ubiquitin-protein ligases, SCF and APC/C

SCF

adds ubiquitin groups so inhibition can't happen

APC/C

controls metaphase/anaphase transition and keeps cell in G1

Cyclin regulation

ubiquitination/degradation and transcription of cyclins

MAPK signaling

increase G1 cyclins when cyclin D binds to CDK4 and activate E2F TFs (G1 ->S)

Retinoblastoma (Rb)

ensures TFs cannot activate expression of cyclin E/A

G1 to S phase steps

mapk signaling increase cyclin D CDK4, cyclin D phosphorylates Rb to release E2F from inhibition, transcription of cyclin E/A, cyclin E?A phosphorylate cdh1, cdh1 inhibits APC/C, SCF polyubiquitinates p27

How does transition to S phase start

phosphorylate Rb, inhibit APC/C, and degrade p27

Steps to S phase

expression of cyclin E/A, stop degrading cyclin E/A from apc/c, and degradation of p27

P27

final switch that controls S phase

Degradation of p27 leads to

DNA replication

How is S phase activated

p27 binds to s cyclin-CDK (inhibited) and polyubiquitinated by SCF to be degraded to release CDK from inhibition

Is p27 degradation reversible

no

G2 -> M

formation of mitotic spindle, chromosomes condense, and disassembly

Wee1

adds inhibitory phosphates (thr/thy) to phosphorylate/inhibit mitotic CDK1

cdc25B

dephosphorylate/activate CDK1

If Wee1 is phosphorylated

inactive and no mitosis

If Wee1 is dephosphorylated

active and mitosis occurs

Cdc25B activate

cyclin B-CDK1

Cyclin B-CDK1 phosphorylates

cdc25C

Pin1 and plk1 ___ cyclin B-CDK1 more

activates

Cyclin B-CDK1 and Plk1 phosphorylate

Wee1

SCF polyubiquitinates

p27 and Wee1

Prophase

chromosomes condense, nuclear envelope breaks down, spindles form

Metaphase

microtubules attach to chromosomes and align

Anaphase

sister chromatids separate

Telophase

nuclear envelope forms, chromosomes decondense back, spindle disassembles

g1/s phase cdk phosphorylate cdh1 inactivating

apc/c

apc/c activity causes unstable

mitotic and s phase cyclins

What polyubiquitination of p27 do

targets p27 for degradation leading to the release of S cyclin CDKs from inhibition

Rb in G1 to S phase

inhibits e2f resulting in inhibition of cyclin A/E transcription

Is cdc dephosphorylates to cyclin B a step from G1 to S phase

no, its G2 to M phase

What is the result of phosphorylation of Rb

e2f TF express cyclin E and A

centrosomes are ____ at start of S phase

duplicated