4: Cell Cycle & Cell Death with factor table

APC/C Mechanism of Action

-Degrades M cyclins via tagging w/ ubiquitins -Targets securin to be destroyed

Cellular Effects of APC/C

-Cell exits mitosis -Cohesins break & chromosomes separate (anaphase)

Wee1 Mechanism of Action

-Inhibitory kinase that adds inhibitory phosphates to M-Cdk

Cellular Effects of Wee1

-Delays mitotic entry

p27 Mechanism of Action

-CKI that binds G1/S Cdks

Cellular Effects of p27

-Prevents progression from G1 to S phase

Cdc25 Mechanism of Action

-Activating phosphatase that removes inhibitory phosphates from Cdks

Cellular Effects of Cdc25

-Triggers mitosis

Rb Protein Mechanism of Action

-Tumor-suppressor protein that binds transcription regulators

Cellular Effects of Rb Protein

-Blocks S-phase gene expression until mitogen triggers G1/S Cdk → phosphorylates Rb to inactivate

p53 Mechanism of Action

1) Activates p21 → binds to G1/S Cdk to prevent S phase 2) Causes apoptosis

Cellular Effects of p53

-Cell death

Cdc6 Mechanism of Action

-Recruited by ORC; both bind helicase

Cellular Effects of Cdc6

-Allows for pre-RC ready to commence replication

S-Cdk Mechanism of Action

1) Activates helicase 2) Starts replication fork formation 3) Phosphorylates Cdc6 and ORC

Cellular Effects of S-Cdk

-Starts the replication fork -Prevents re-replication

M-Cdk Mechanism of Action

-Cdc25 removes the inhibitory phosphate

Cellular Effects of M-Cdk

-Allows for entry into M phase

Securin Mechanism of Action

-Prevents breakage of cohesins by inactivating separase

Cellular Effects of Securin

-Destroyed by APC/C to allow separase to break cohesins

Separase Mechanism of Action

-Breaks cohesins between sister chromatids

Cellular Effects of Separase

-Allows entry into anaphase

RhoA Mechanism of Action

-Regulates assembly and contraction of the actomyosin ring

Cellular Effects of RhoA

-Ensures correct positioning of the cleavage furrow

Bax/Bak Mechanism of Action

-Regulates apoptosis by inducing release of cytochrome c that activates initiators

Cellular Effects of Bax/Bak

-Promotes apoptosome assembly that recruits procaspase-9 for apoptosis

Cell Cycle

Ordered sequence of events that allows a cell to grow, replicate its DNA, and divide into two identical daughter cells.

M Phase

Phase of the cell cycle that includes mitosis and cytokinesis.

Interphase

Portion of the cell cycle between M phases; encompasses G1, S, and G2 phases and accounts for cell growth and DNA replication.

G1 Phase

Gap phase in which the cell grows and assesses conditions before committing to DNA synthesis.

S Phase

Synthesis phase in which DNA replication occurs.

G2 Phase

Second gap phase allowing cell growth and verification that DNA is fully replicated before mitosis.

Cell-Cycle Checkpoint

Regulatory point that can delay the cycle until certain conditions (DNA integrity, nutrient supply, spindle attachment) are met.

Cyclin

Regulatory protein whose concentration fluctuates cyclically and whose binding activates Cdks.

Cyclin-Dependent Kinase (Cdk)

Serine/threonine kinase that drives cell-cycle transitions when bound to a cyclin.

Cyclin-Cdk Complex

Active enzyme complex formed by a cyclin bound to its partner Cdk, responsible for triggering specific cell-cycle events.

M Cyclin

Cyclin that associates with Cdk1 to drive entry into mitosis.

S Cyclin

Cyclin that partners with Cdks to initiate DNA replication.

G1 Cyclin

Cyclin that helps cells progress through G1 and prepare for the G1/S transition.

Anaphase-Promoting Complex (APC/C)

Ubiquitin ligase that targets M cyclins and securin for destruction, promoting exit from mitosis and onset of anaphase.

Wee1 Kinase

Inhibitory kinase that adds inhibitory phosphates to M-Cdk, delaying mitotic entry.

Cdc25 Phosphatase

Activating phosphatase that removes inhibitory phosphates from Cdks to trigger mitosis.

Cdk Inhibitor (CKI)

Protein that binds Cyclin-Cdk complexes to block their activity.

p27

CKI that binds G1/S-Cdks to prevent progression into S phase.

G0 Phase

Quiescent state in which a cell has withdrawn from the cell cycle, either temporarily or permanently.

Mitogen

Extracellular signal that stimulates cell division by promoting production of G1 and G1/S cyclins.

Retinoblastoma (Rb) Protein

Tumor-suppressor protein that binds transcription regulators to block S-phase gene expression until phosphorylated by Cdks.

p53

DNA-damage-activated transcription factor that induces expression of genes such as p21 and can trigger apoptosis.

p21

CKI transcribed in response to p53; inhibits G1/S- and S-Cdks after DNA damage.

Origin Recognition Complex (ORC)

Protein complex that binds replication origins and helps assemble the pre-replicative complex in early G1.

Pre-Replicative Complex (pre-RC)

Assembly of ORC, Cdc6, and helicase at replication origins, licensing them for DNA replication.

Cohesin

Protein ring that holds sister chromatids together from S phase until anaphase.

Mitotic Spindle

Microtubule-based structure that segregates duplicated chromosomes during mitosis.

Contractile Ring

Actin–myosin filament ring that constricts the cell membrane to complete cytokinesis.

Aster

Radial array of microtubules emanating from each centrosome during mitosis.

Prophase

First stage of mitosis in which chromosomes condense and the spindle begins to form.

Prometaphase

Mitotic stage marked by nuclear envelope breakdown and attachment of microtubules to kinetochores.

Kinetochore

Protein complex assembled on the centromere that links each chromatid to spindle microtubules.

Metaphase

Mitotic stage in which chromosomes align at the spindle equator.

Anaphase

Stage when sister chromatids separate and move toward opposite spindle poles.

Interpolar Microtubule

Spindle microtubule that overlaps with its counterpart from the opposite pole, helping stabilize the spindle.

Astral Microtubule

Spindle microtubule that radiates toward the cell cortex, helping position the spindle.

Separase

Protease that cleaves cohesin to trigger chromatid separation at anaphase.

Securin

Inhibitory protein that binds separase; destroyed by APC/C to allow anaphase onset.

Spindle Assembly Checkpoint

Control system that delays anaphase until all chromosomes are properly attached to the spindle.

Telophase

Mitotic stage when chromosomes arrive at poles and new nuclear envelopes reform.

Cytokinesis

Division of the cytoplasm into two daughter cells, usually mediated by the contractile ring.

RhoA

Small GTPase that regulates assembly and contraction of the contractile ring during cytokinesis.

Apoptosis

Programmed cell death involving caspase activation and orderly dismantling of cellular components.

Caspase

Cysteine-aspartate protease that mediates the biochemical events of apoptosis.

Procaspase

Inactive caspase precursor that must be cleaved to become an active enzyme.

Bcl2 Family

Group of proteins that regulate apoptosis, including both pro- and anti-apoptotic members.

Bax

Pro-apoptotic Bcl2 family protein that promotes cytochrome-c release from mitochondria.

Bak

Pro-apoptotic Bcl2 family protein acting similarly to Bax to trigger apoptosis.

Apoptosome

Protein complex formed after cytochrome-c release that activates initiator caspase-9.

Survival Factor

Extracellular signal that suppresses apoptosis in target cells.

Growth Factor

Extracellular molecule that stimulates cell growth by increasing protein synthesis and reducing degradation.

Gamete

Haploid reproductive cell (sperm or egg) produced by meiosis.

Zygote

Diploid cell formed by fusion of two haploid gametes.

Homologous Chromosome

Pair of chromosomes, one maternal and one paternal, carrying the same genes in the same order.

Meiosis

Two-round reductive cell division that produces haploid gametes from diploid germ cells.

Chiasma (plural Chiasmata)

Visible crossover site where non-sister chromatids exchange DNA during meiosis I.

Crossover

Reciprocal genetic exchange between non-sister chromatids that increases genetic diversity.

Bivalent

Structure of paired homologous chromosomes (each duplicated) aligned during meiosis I.

Nondisjunction

Failure of homologous chromosomes or sister chromatids to separate properly during meiosis or mitosis.

Aneuploidy

Abnormal number of chromosomes in a cell, often resulting from nondisjunction.