Cell Cycle, Mitosis, and DNA Replication: Key Concepts and Regulation (CH18)

Major phases of the cell cycle

G1, S, G2, and M phase.

Phase where DNA replication occurs

S phase.

When cells rest outside the cycle

G0 phase.

Why cell-cycle progression must be ordered

Ensures DNA is replicated once and chromosomes segregate correctly.

Cell-cycle checkpoints

G1, G2, and M checkpoints; ensure DNA integrity, replication completion, and spindle attachment.

What Cdks are

Cyclin-dependent kinases that phosphorylate proteins to drive the cell cycle.

What cyclins are

Regulatory proteins whose levels rise and fall to activate Cdks.

Major cyclin-Cdk complexes

G1-Cdk, G1/S-Cdk, S-Cdk, M-Cdk; each triggers specific cell-cycle steps.

How cyclin-Cdk complexes are regulated

By cyclin levels, phosphorylation, dephosphorylation, and Cdk inhibitors.

Effect of phosphorylation on M-Cdk

Inhibitory phosphorylation keeps M-Cdk inactive until removed.

How mitotic Cdk is activated

Cdc25 removes inhibitory phosphates, triggering positive feedback.

Role of Wee1 kinase

Adds inhibitory phosphates to M-Cdk.

Role of Cdc25 phosphatase

Removes inhibitory phosphates to activate M-Cdk.

Effect of p27 inhibitor

Binds and inactivates cyclin-Cdk complexes.

What APC/C stands for

Anaphase-Promoting Complex/Cyclosome.

How APC/C works

Tags securin and cyclins with ubiquitin for degradation.

Role of ubiquitin in cyclin destruction

Marks cyclins for proteasomal degradation.

What triggers M-phase to G1 transition

APC/C-mediated destruction of M-cyclin.

What mitogens are

Signals that stimulate cell division by promoting cyclin production.

Role of Rb protein

Tumor suppressor that inhibits transcription factors for S-phase entry.

How mitogens affect Rb

Mitogens activate Cdks that phosphorylate Rb, releasing transcription factors.

How DNA damage pauses the cycle

p53 activates p21, which inhibits G1/S-Cdk and S-Cdk.

How the cell ensures one DNA copy

Origins licensed only in G1; S-Cdk prevents re-licensing.

How DNA is proofread

DNA polymerase 3'→5' exonuclease activity.

How DNA is corrected

Mismatch repair removes and replaces incorrect bases.

How S-Cdk initiates replication

Phosphorylates pre-RC components to start DNA synthesis.

How S-Cdk prevents re-replication

Phosphorylates ORC and Cdc6 to block new pre-RC formation.

Role of ORC Origin Recognition Complex;

binds replication origins.

Role of Cdc6

Helps load helicase to form pre-RC.

What must happen before nuclear division

DNA replication, chromosome condensation, spindle assembly, centrosome duplication.

How M-Cdk mediates G2→M transition

Phosphorylates proteins for mitotic entry.

How cell pauses if replication incomplete

Inhibits Cdc25 to prevent M-Cdk activation.

How M-Cdks help exit M-phase

Activate APC/C to destroy M-cyclin.

Stages of M-phase

Prophase, prometaphase, metaphase, anaphase, telophase, cytokinesis.

Mother cell

Original cell before division.

Daughter cells

Two cells produced after division.

Sister cells

The two daughter cells.

Chromatids

Identical copies of a chromosome.

Chromosomes

DNA molecules packaged with proteins.

What cohesins are

Rings that hold sister chromatids together.

Function of cohesins

Maintain chromatid pairing until anaphase.

What condensins are

Proteins that compact chromosomes.

Function of condensins

Condense chromosomes for segregation.

Stage when nuclear envelope disassembles

Prometaphase.

Stage when nuclear envelope reassembles

Telophase.

How nuclear envelope disassembles

Phosphorylation of lamins and pore proteins.

How nuclear envelope reassembles

Dephosphorylation of lamins and pore proteins.

What the mitotic spindle is

Microtubule-based machine that segregates chromosomes.

How the spindle works

Microtubules attach to kinetochores and pull chromatids apart.

How microtubules grow and shrink

Through dynamic instability.

What a kinetochore is

Protein complex at centromere where microtubules attach.

Three types of spindle microtubules

Astral, kinetochore, interpolar.

Role of APC/C in chromatid separation

Degrades securin to activate separase.

Molecular process of chromatid separation

Securin destroyed → separase cleaves cohesins.

Role of securin

Inhibits separase.

Role of separase

Cleaves cohesins to separate chromatids.

What happens if chromosomes attach improperly

Checkpoint blocks anaphase; errors cause aneuploidy.

How plant cells form new cell wall

Vesicles fuse to form cell plate during cytokinesis.

What apoptosis is

Programmed cell death.

How apoptosis works

Caspases dismantle the cell in a controlled manner.

Why apoptosis is important

Removes damaged or unnecessary cells; shapes tissues.

What caspases are

Proteases that execute apoptosis.

How caspases are used

Initiator caspases activate executioner caspases.

Types of caspases

Initiator (e.g., 8, 9) and executioner (e.g., 3, 7).

Intrinsic apoptosis regulation

Bcl-2 family controls mitochondrial permeabilization.

Intrinsic pathway mechanism

Bax/Bak release cytochrome c → apoptosome → caspase-9.

Extrinsic apoptosis activation

Death receptors bind ligands to activate caspases.

How survival factors work

Suppress apoptosis by increasing Bcl-2 or inhibiting pro-apoptotic proteins.

What growth factors are

Signals that promote cell growth by increasing protein synthesis.

Signals that inhibit survival or growth

Anti-growth factors or death ligands.

What cytokinesis is

Division of cytoplasm into two daughter cells.

How cytokinesis occurs in animals

Contractile ring of actin and myosin pinches cell.

How spindle determines cleavage plane

Spindle position dictates contractile ring placement.

How contractile ring divides cell

Actin-myosin contraction tightens ring to split cell.