Cell cycle Study Guide

📖 Core Concepts Cell Cycle – Ordered series of events that lead a cell to divide into two daughter cells. Interphase (G1‑S‑G2) – Growth, DNA replication, and preparation for mitosis. M Phase – Mitosis (nuclear division) + cytokinesis (cytoplasmic division). G0 (Quiescence) – A reversible resting state; differentiated neurons stay here permanently. Cyclins & CDKs – Cyclins are regulatory subunits; CDKs are catalytic subunits that phosphorylate targets. Specific cyclin‑CDK pairs fire at each transition (e.g., Cyclin D‑CDK4/6 → G1, Cyclin E‑CDK2 → G1/S, Cyclin B‑CDK1 → M). Checkpoints – Surveillance mechanisms: G1/S (restriction point), G2/M, Metaphase‑Spindle Assembly, plus a Go checkpoint for entry into the cycle. p53 – Tumor‑suppressor that activates DNA‑repair or apoptosis at G1/S and G2/M; loss permits damaged cells to divide. Cytokinesis Modes – Animal cells form a cleavage furrow; plant cells assemble a cell plate. Prokaryotic Division – B, C, D periods; Z‑ring (FtsZ) defines the division site. Archaeal Division – Uses CdvA/ESCRT‑III polymers or FtsZ1/FtsZ2 rings; lacks a true G0 phase. --- 📌 Must Remember Restriction point (START) = G1 checkpoint; passes when G1 cyclin‑CDKs (Cyclin D‑CDK4/6) phosphorylate Rb → partial E2F release. Rb phosphorylation cascade: Cyclin D‑CDK4/6 → hypo‑phosphorylated Rb → partial E2F release → Cyclin E expression. Cyclin E‑CDK2 → hyper‑phosphorylated Rb → full E2F activation → S‑phase entry. S‑phase: DNA content doubles; chromosome number stays constant (each chromosome → two sister chromatids). G2 checkpoint relies heavily on p53; dysfunctional p53 → cancer risk. M‑phase entry: Cyclin B‑CDK1 activation → nuclear envelope breakdown (open mitosis) or spindle assembly (closed mitosis). CDK inhibitors: p21 (p53‑induced), p27 (TGF‑β‑induced), p16‑INK4a (INK4a/ARF family). FDA‑approved CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) treat HR⁺/HER2⁻ breast cancer. Radiosensitivity: Most sensitive in late M & G2; most resistant in late S. Prokaryotic Z‑ring = filamentous temperature‑sensitive (FtsZ) protein scaffold for cytokinesis. Archaeal division: CdvA‑ESCRT‑III or FtsZ1/FtsZ2 rings; proteasome‑mediated proteolysis is essential. --- 🔄 Key Processes Eukaryotic Cell‑Cycle Progression G1 → S: Cyclin D‑CDK4/6 phosphorylates Rb → Cyclin E‑CDK2 completes Rb phosphorylation → E2F activates S‑phase genes. S: Pre‑replication complexes fire; DNA polymerases duplicate each chromosome. G2 → M: Cyclin B‑CDK1 accumulates, triggers nuclear envelope breakdown & spindle formation. M (Mitosis): Prophase → Prometaphase → Metaphase → Anaphase → Telophase. Cytokinesis: Animal – cleavage furrow; Plant – cell plate formation. Checkpoint Activation G1/S: Growth‑factor signals → cyclin D expression → Rb phosphorylation. G2/M: DNA‑damage detection → p53 → transcription of repair genes or apoptosis. Spindle Assembly: Unattached kinetochores → “wait‑anaphase” signal → inhibit APC/C, blocking anaphase. Bacterial Cytokinesis (FtsZ) FtsZ polymerizes → Z‑ring at mid‑cell → recruits divisome proteins → constricts to split cell. Archaeal Cytokinesis CdvA/ESCRT‑III route: CdvA + CdvB assemble → membrane remodeling → division. FtsZ route: FtsZ1/FtsZ2 form a contractile ring → constriction. --- 🔍 Key Comparisons Eukaryote vs Prokaryote Cell Cycle Eukaryote: Interphase (G1‑S‑G2) + M phase; regulated by cyclin‑CDK complexes. Prokaryote: B (birth), C (DNA synthesis), D (division) periods; driven by FtsZ ring formation. Open vs Closed Mitosis Open (animals): Nuclear envelope breaks down in prophase. Closed (fungi): Nuclear envelope remains intact throughout mitosis. Cyclin D vs Cyclin E Action Cyclin D‑CDK4/6: Mono‑phosphorylates Rb (hypo‑phosphorylation) → partial E2F release. Cyclin E‑CDK2: Hyper‑phosphorylates Rb → full E2F release → S‑phase entry. CDK4/6 Inhibitors vs General CDK Blockers CDK4/6 inhibitors: Specific for cyclin D‑CDK4/6; used clinically in breast cancer. Broad CDK inhibitors: Target multiple CDK–cyclin pairs; higher toxicity. Bacterial Z‑ring vs Archaeal CdvA/ESCRT‑III Z‑ring: Tubulin‑like filament, directly scaffolds division machinery. CdvA/ESCRT‑III: Membrane‑remodeling complex, analogous to eukaryotic cytokinesis. --- ⚠️ Common Misunderstandings DNA content vs chromosome number: In S phase DNA doubles but the chromosome count stays the same (each becomes two sister chromatids). p53 only triggers apoptosis: It also activates DNA‑repair pathways and cell‑cycle arrest at G1/S and G2/M. All cyclins act the same: Each cyclin pairs with specific CDKs and acts at distinct checkpoints (D → G1, E → G1/S, A → S, B → M). G0 is a “phase” of division: G0 is a true exit from the cycle; cells are not progressing toward division. CDK1 is redundant in all organisms: Yeast and plants can survive CDK1 loss; in animals CDK1 is essential. --- 🧠 Mental Models / Intuition Cyclin‑CDK as a “fuel pump”: When the right cyclin binds a CDK, the pump turns on, delivering phosphate “fuel” to drive the next stage. Checkpoints as security gates: Each gate only opens when the “ID” (e.g., sufficient nutrients, intact DNA, proper spindle attachment) is verified. Rb‑E2F switch as a light dimmer: Partial phosphorylation turns the light on low (Cyclin D), full phosphorylation turns it full‑bright (Cyclin E). Z‑ring vs CdvA/ESCRT‑III as construction crews: One builds a scaffold (Z‑ring), the other uses a demolition crew (ESCRT‑III) to cut the membrane. --- 🚩 Exceptions & Edge Cases Closed mitosis (fungi): Nuclear envelope never disassembles, altering spindle‑microtubule dynamics. Plant cytokinesis: No cleavage furrow; a new cell plate forms from vesicle fusion. Archaeal cell cycle: No true G0; cells can pause in G2 under stress (e.g., TACK archaea). Late‑S radiosensitivity: Cells are actually more resistant in late S, contrary to the “more DNA = more damage” intuition. CDK1 essentiality: Lethal knockout in animals but not in yeast or Arabidopsis (CDKA;1 mutants viable). --- 📍 When to Use Which Identify the checkpoint being tested: Growth‑factor dependent → think G1/S (cyclin D‑CDK4/6, Rb). DNA‑damage → focus on G2/M (p53, apoptosis). Spindle‑attachment → Metaphase checkpoint (APC/C inhibition). Choosing a therapeutic context: Hormone‑receptor‑positive breast cancer → CDK4/6 inhibitors. General proliferative disease → broader CDK inhibition (higher toxicity). Distinguishing division types in questions: Animal cell: look for cleavage furrow, open mitosis. Plant cell: look for cell plate, pre‑prophase band. Bacterial: mention FtsZ Z‑ring. Archaeal: mention CdvA/ESCRT‑III or FtsZ1/FtsZ2 ring. --- 👀 Patterns to Recognize Phosphorylation cascade → checkpoint passage (Rb → E2F, Whi5 → SBF). Double‑negative feedback → bistable switch at G1/S (CDK activity inhibits its own inhibitor). “Wait‑anaphase” signal appears only when any kinetochore is unattached → APC/C remains inactive. Radiosensitivity peaks in phases where DNA is most exposed (late M, G2). Cyclin expression timing matches the phase it controls (e.g., Cyclin B peaks just before mitosis). --- 🗂️ Exam Traps Confusing DNA content with chromosome number – Remember chromosomes stay constant during S; only DNA amount changes. Assuming p53 is only a tumor suppressor for apoptosis – It also enforces G1/S and G2/M arrests. Mixing up G0 and G1 – G0 is a permanent/quiescent exit; G1 is preparatory and still part of the cycle. Believing all cyclin‑CDK complexes are interchangeable – Specificity matters; wrong cyclin‑CDK pair will not trigger the correct transition. Thinking CDK1 knockout is lethal in all organisms – Viable in yeast and Arabidopsis; essential only in animals. Selecting “late‑S” as the most radiosensitive phase – The opposite is true; late S is relatively resistant. ---