Chapter 17: Cell Cycle & Mitosis

What are the phases of the cell cycle?

G1, S, G2, M

What is the Mitosis (Stage 1) steps?

1. Prophase

2. Prometaphase

3. Metaphase

4. Anaphase

5. Telophase

6. Cytokinesis

What does M-Cdk do?

Triggers entry into mitosis

What does cohesin do?

Holds sister chromatids together

What does condensin do?

Compacts chromosomes

What are the 3 spindle microtubules?

Astral, kinetochore, interpolar

What is biorientation?

Sister kinetochores attach to opposite poles

What stabilizes correct attachment?

Tension

What happens if attachment is incorrect?

Destabilized and retried

What is APC/C?

Ubiquitin ligase that triggers anaphase

What does APC/C destroy?

Securin

What does securin do?

Inhibits separase

What does separase do?

Cleaves cohesin

What happens if cohesin is not cleaved?

Chromatids cannot separate

What is the spindle assembly checkpoint?

Blocks anaphase if kinetochores unattached

Anaphase A

Chromosomes move toward poles

Anaphase B

Spindle poles move apart

What happens in telophase?

Nuclear envelope reforms

What drives cytokinesis?

Actin + myosin II ring

What activates cell cycle entry?

Mitogens

Mitogen pathway

Ras → MAPK → Myc → cyclin

What does Rb do?

Inhibits E2F

What does phosphorylation of Rb do?

Releases E2F

What does E2F do?

Activates S-phase genes

What happens if Rb cannot be phosphorylated?

S phase blocked

What does p53 do?

Activates p21 in response to DNA damage

What does p21 do?

Inhibits Cdks

What happens with DNA damage?

Cell cycle arrest

What is the restriction point?

Commitment point in G1 after which the cell proceeds into S phase

What is G0?

Nondividing state; can be permanent or long-term quiescent

Can embryonic cells lack G1?

Yes, rapidly dividing embryonic cells may lack a G1 phase

What is mitosis?

Nuclear division that separates sister chromatids into daughter nuclei

What causes nuclear envelope breakdown in mitosis?

M-Cdk-dependent phosphorylation of lamins

What are DNA catenations?

DNA interlinks/knots that also contribute to sister chromatid cohesion

What do astral microtubules do?

Help position the spindle

What do interpolar/overlap microtubules do?

Help push spindle poles apart

What do kinetochore microtubules do?

Attach chromosomes to spindle poles

What is search-and-capture?

Dynamic spindle microtubules randomly encounter and attach kinetochores

What kind of kinetochore attachment often happens first?

Lateral attachment

How is correct biorientation stabilized?

Balanced tension across sister kinetochores

What happens to low-tension incorrect attachments?

They are destabilized and retried

What three kinetochore properties promote biorientation from the practice key?

Back-to-back orientation, stabilization of plus ends, and tension sensing/error correction

What does the spindle assembly checkpoint monitor?

Whether kinetochores are properly attached

What happens if one kinetochore is unattached?

APC/C is inhibited and anaphase is delayed

What are the two main events of anaphase A?

Sister chromatid separation and chromosome movement toward poles

What shortens during anaphase A?

Kinetochore microtubules

At what ends can kinetochore microtubules shorten in anaphase A?

Both plus and minus ends

What happens in anaphase B?

Spindle poles move farther apart

How do kinesins contribute to anaphase B?

Crosslink overlap microtubules and slide them apart

How do dyneins contribute to anaphase B?

Cortex-attached dyneins pull on astral microtubules

What reforms in telophase?

Nuclear envelope and daughter nuclei

What forms the contractile ring in cytokinesis?

Actin and myosin II

What happens to actin subunits during ring constriction?

Actin subunits are lost as the ring constricts

How can S phase be experimentally detected?

BrdU incorporation into newly synthesized DNA

What does doubled DNA content indicate?

S phase or post-replication DNA content

General rule for Cdks

Cdks require cyclin binding to be active

What else can inhibit Cdks besides lack of cyclin?

Inhibitory phosphorylation and CKI proteins

What happens in late M/early G1 to keep G1 stable?

APC/C destroys cyclins, CKIs accumulate, cyclin gene expression falls

Name two example mitogens from the notes

PDGF and EGF

What signaling pathway connects mitogens to cyclin production?

Ras → MAP kinase → Myc

What positive feedback helps drive G1 into S phase?

G1/S-Cdk and S-Cdk further phosphorylate Rb

What major growth pathways support proliferation?

PI 3-kinase and TOR