4.6 Regulation of the Cell Cycle

Cell cycle checkpoints are internal control points (G1, G2, and the spindle assembly checkpoint) that pause progression so the cell can verify conditions: DNA integrity, complete replication, and correct chromosome attachment to the spindle. Checkpoints work through regulatory proteins—cyclins and cyclin-dependent kinases (CdKs)—and tumor suppressors like p53 that can halt the cycle or trigger apoptosis if damage is irreparable (EK 4.6.A.1–A.2; LO 4.6.A/B). Cells need checkpoints to prevent propagation of mutations; without them you get uncontrolled division or programmed cell death, which links to cancer when checkpoints are disrupted (EK 4.6.B.1). For AP exam review, focus on the roles of G1/G2/spindle checkpoints, cyclin–CdK regulation, and outcomes of disruption. Review Fiveable’s Topic 4.6 study guide for concise examples (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and try practice questions (https://library.fiveable.me/practice/ap-biology).

Cyclins are proteins whose levels rise and fall during the cell cycle; cyclin-dependent kinases (Cdks) are enzymes that need cyclins to become active. When a cyclin binds a Cdk, the complex phosphorylates target proteins that drive specific cell-cycle events (e.g., starting DNA replication or triggering mitosis). Checkpoints (G1, G2, spindle) monitor DNA integrity, chromosome attachment, and cell size; if problems appear, checkpoint pathways block cyclin–Cdk activity (or raise CDK inhibitors) so the cycle pauses. Damage sensors like p53 can increase CDK inhibitors or trigger apoptosis if damage’s severe. Cyclins are removed by targeted degradation (ubiquitin/proteasome), which inactivates Cdks and lets the next phase proceed. This regulation prevents uncontrolled division (cancer) or forces programmed cell death when needed—exactly what EK 4.6.A.1 and EK 4.6.A.2 describe. For a quick review, see the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and more unit resources (https://library.fiveable.me/ap-biology/unit-4). Practice problems: https://library.fiveable.me/practice/ap-biology.

Apoptosis is programmed, orderly cell suicide: the cell activates internal signaling (often via p53 if DNA damage is sensed at checkpoints), turns on caspases, shrinks, fragments its nucleus and membrane into tidy apoptotic bodies that phagocytes clear without inflammation. It’s a regulated response to irreparable damage or developmental cues and is listed in the CED under disruptions to the cell cycle (EK 4.6.B.1). “Regular” cell death usually refers to necrosis—an uncontrolled response to severe injury (trauma, toxins, lack of blood). Necrotic cells swell and burst, leaking contents and causing inflammation; it’s messy and not driven by cyclin/CdK checkpoint signaling. For AP exam focus: understand checkpoints, p53, CDK inhibitors, and that apoptosis is a programmed outcome when checkpoints detect problems (LO 4.6.A and LO 4.6.B). For a clear Topic 4.6 review, see the unit 4 cell cycle study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP). For extra practice, check Fiveable’s AP Bio practice problems (https://library.fiveable.me/practice/ap-biology).

Checkpoints (G1, G2, spindle) use internal signals—cyclins + CdKs, tumor suppressors (like p53, Rb) and CDK inhibitors—to pause the cycle for DNA repair or to trigger apoptosis. If checkpoints fail (because tumor suppressors are mutated or proto-oncogenes become oncogenes), cells with DNA damage keep dividing. That lets mutations accumulate (genomic instability), cells evade apoptosis, and growth signals become unchecked → a mass of abnormal cells: cancer. On the AP exam, connect checkpoint failure to both cancer and apoptosis (EK 4.6.B.1) and mention cyclin–CdK control (EK 4.6.A.2). Key words to use: G1/G2/spindle checkpoint, p53, tumor suppressors, proto-oncogenes → oncogenes, CDK inhibitors, caspases (apoptosis). If you want a quick refresher, see the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and try practice questions at Fiveable (https://library.fiveable.me/practice/ap-biology).

Cells have multiple checkpoints because accurate division is essential—one mistake can cause damaged DNA, unequal chromosomes, or uncontrolled growth (cancer) or trigger apoptosis. Checkpoints (G1, G2, spindle) act as internal controls (LO 4.6.A) that verify DNA integrity, proper replication, and correct spindle attachment before the cell proceeds. Cyclins bind CDKs to drive the cycle only when conditions are right; tumor suppressors (like p53) and CDK inhibitors stop progression if damage is detected so repair can occur or apoptosis can be triggered (LO 4.6.B). Having several checkpoints means errors get caught at different stages (before S phase, before mitosis, and during chromosome segregation), reducing the chance that a single failure causes big problems. For review, see the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and the Unit 4 overview (https://library.fiveable.me/ap-biology/unit-4). Practice questions are at (https://library.fiveable.me/practice/ap-biology).

Internal controls are checkpoints and molecular signals inside the cell that monitor DNA integrity and readiness to progress (EK 4.6.A.1). Examples you should know for the AP exam: the G1 and G2 checkpoints and the spindle assembly checkpoint; cyclins + cyclin-dependent kinases (CdKs) drive transitions (EK 4.6.A.2). Internal sensors (like p53 or retinoblastoma protein—tumor suppressors) can pause the cycle, activate CDK inhibitors, or trigger apoptosis if damage’s irreparable (LO 4.6.A, LO 4.6.B). External controls are signals from outside the cell that influence whether a cell enters the cycle—e.g., growth factors, contact inhibition, or nutrient availability. They bind receptors and start signal transduction that alters cyclin/Cdk activity (Topic 4.1–4.3 links to signaling help). Disruption of either type can cause unchecked division (oncogenes/proto-oncogenes) or cell death (apoptosis), which is exactly what LO 4.6.B covers. For review, see the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and the Unit 4 overview (https://library.fiveable.me/ap-biology/unit-4). Practice questions: (https://library.fiveable.me/practice/ap-biology).

Cyclin levels rise and fall in a cycle to control when Cdks (cyclin-dependent kinases) are active. Different cyclins are synthesized in specific phases (increase in G1 and again in G2) so they bind Cdks and activate them at checkpoints (G1, G2, spindle checkpoint) to push the cell into S phase or M phase. After a transition, cyclins are tagged for degradation (ubiquitin/proteasome), so Cdk activity drops and the next stage can proceed in order. This timed buildup-and-breakdown enforces internal controls described in EK 4.6.A.2 and checkpoints in LO 4.6.A: it ensures DNA is replicated and chromosomes are correctly attached before division; disruptions can cause failed checkpoints, leading to apoptosis or cancer (EK 4.6.B.1). Want a refresher tied to AP topics? Check the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and try practice questions (https://library.fiveable.me/practice/ap-biology).

Not contradictory—it depends how the cell-cycle controls are disrupted. If checkpoints or regulators (cyclins/Cdks, tumor suppressors like p53 or Rb) are partially lost or mutated so the “stop” signals fail, cells can divide uncontrollably and form cancer (proto-oncogenes → oncogenes; loss of tumor suppressors). But if damage is severe or the DNA-damage response is intact, checkpoint sensors (like p53) trigger apoptosis through caspases to remove the damaged cell. So: mild/targeted failure of checkpoints → uncontrolled proliferation (cancer); massive DNA damage or strong checkpoint activation → programmed cell death (apoptosis). AP CED keywords that matter here: checkpoints, cyclins/CdKs, p53, tumor suppressors, oncogenes, apoptosis (EK 4.6.A.1, EK 4.6.A.2, EK 4.6.B.1). For a concise review and practice questions on this topic, see the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and more unit resources (https://library.fiveable.me/ap-biology/unit-4).

There are three major cell-cycle checkpoints you should know (CED LO 4.6.A / EK 4.6.A.1): - G1 (restriction) checkpoint—checks for favorable external conditions, growth factors, sufficient cell size and intact DNA before S phase. If DNA is damaged, p53 helps pause the cycle and can trigger DNA repair or apoptosis. - G2 checkpoint—checks that DNA replication is complete and undamaged, and that the cell has enough resources to enter mitosis. Problems here delay entry to M phase. - M (spindle assembly) checkpoint—during mitosis it checks that all chromosomes are properly attached to the spindle and aligned at the metaphase plate so sister chromatids segregate correctly. Control is driven by cyclins and cyclin-dependent kinases (EK 4.6.A.2); disruptions (failed checkpoints or mutated tumor suppressors/proto-oncogenes) can lead to cancer or apoptosis (EK 4.6.B.1). For a quick AP-friendly review, see the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP). For broader unit review and practice, check the Unit 4 page (https://library.fiveable.me/ap-biology/unit-4) and the practice question bank (https://library.fiveable.me/practice/ap-biology).

Cyclins are proteins whose levels go up and down during the cell cycle; CDKs (cyclin-dependent kinases) are enzymes that need a cyclin partner to become active. When a specific cyclin accumulates, it binds a CDK and activates it; the active cyclin–CDK complex then phosphorylates target proteins that drive the cell from one phase to the next (for example, past the G1 checkpoint into S or past G2 into mitosis). Checkpoints (G1, G2, spindle-assembly) monitor DNA damage, replication, and chromosome attachment; if something’s wrong, checkpoint signals stop cyclin–CDK activity (or activate CDK inhibitors) so the cell pauses, repairs, or triggers apoptosis. Disruption of these controls can lead to uncontrolled division (cancer) or cell death—topics the AP tests under EK 4.6.A.2 and EK 4.6.B.1. For a concise Topic 4.6 review and practice, see the Fiveable cell-cycle study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and practice questions (https://library.fiveable.me/practice/ap-biology).

Programmed cell death (apoptosis) is crucial because it removes cells that are damaged, infected, or no longer needed—so tissues develop and stay healthy without causing inflammation. It’s triggered when internal checkpoints detect problems the cell can’t fix (like severe DNA damage, often sensed by p53), when developmental programs require sculpting (e.g., fingers forming), or when cells receive external death signals. Mechanistically, caspases execute apoptosis after upstream signals activate the pathway. On the AP CED this links to cell-cycle regulation and disruptions: failing checkpoints can lead either to uncontrolled growth (cancer) or to apoptosis (EK 4.6.A.1, EK 4.6.B.1). For exam prep, know checkpoint roles (G1, G2, spindle), that cyclin–CDK interactions regulate progression, and that apoptosis is a programmed response to irreparable damage. For a focused review, see the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and practice questions (https://library.fiveable.me/practice/ap-biology).

Cancer cells bypass checkpoints by breaking the internal controls the CED describes. Normally cyclins + cyclin-dependent kinases (CdKs) drive the cycle and checkpoints (G1, G2, spindle) use tumor suppressors and DNA-damage responses to pause or trigger apoptosis. Cancer cells do this by: mutating proto-oncogenes into oncogenes so signaling for cyclin/CdK activity is always on; losing tumor suppressors (like p53 or Rb) so damaged DNA isn’t detected or halted; downregulating CDK inhibitors; and avoiding apoptosis (so caspases aren’t activated). They can also upregulate telomerase and alter DNA-repair pathways to keep dividing. These disruptions match LO 4.6.A/B: checkpoints + cyclin–CdK control, and how disruptions lead to cancer or failed apoptosis. For a quick topic review, see the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP). For full unit review or practice problems, check the Unit 4 page (https://library.fiveable.me/ap-biology/unit-4) and practice bank (https://library.fiveable.me/practice/ap-biology).

Cell-cycle regulation and DNA damage repair are tightly linked: checkpoints (especially G1 and G2) pause the cycle so repair can occur. DNA damage activates sensors that stabilize p53, which upregulates CDK inhibitors and halts cyclin–CDK activity (EK 4.6.A.1–A.2). That pause gives repair machinery time to fix lesions; if damage is too severe, p53 also helps trigger apoptosis (EK 4.6.B.1). Disruptions in these controls—lost tumor suppressors (like p53) or overactive proto-oncogenes—let cells divide with unrepaired DNA, increasing cancer risk (CED keywords: checkpoints, cyclins, CDK inhibitors, p53, tumor suppressors, apoptosis). For AP exam purposes, you should be able to describe checkpoint roles and link failures to cancer or apoptosis (LO 4.6.A, LO 4.6.B). For a quick review, check the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and try related practice questions (https://library.fiveable.me/practice/ap-biology).

You’ll want to master three core ideas for LO 4.6 on the AP exam: - Checkpoints control cycle progression: G1 (is environment/DNA OK?), G2 (is DNA replicated/undamaged?), and the spindle assembly checkpoint (are chromosomes attached to spindle?). These are internal controls that can pause the cycle (EK 4.6.A.1). - Cyclins + cyclin-dependent kinases (CdKs) drive transitions: changing cyclin levels activate CdKs to push the cell past checkpoints (EK 4.6.A.2). Don’t memorize specific cyclin-CdK pairs—just know the interaction and regulatory idea. - What happens when control breaks down: failure of checkpoints or mutated tumor suppressors (like p53/retinoblastoma protein) or activated proto-oncogenes → uncontrolled division (cancer) or triggered apoptosis (caspase pathways). Be able to identify disruptions and predict effects (EK 4.6.B.1). On the exam expect multiple-choice and FRQ items linking these concepts to experimental data (Unit 4 is ~10–15% of MCQs). Review the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP) and practice questions (https://library.fiveable.me/practice/ap-biology).

Cells use built-in checkpoints and molecular signals to decide if it’s safe to move on. At the G1 checkpoint the cell checks growth signals, nutrients and DNA integrity—if DNA is damaged, tumor suppressors like p53 (and CDK inhibitors) halt progress or trigger apoptosis. Cyclins bind cyclin-dependent kinases (CdKs) to drive transitions (G1→S, G2→M); only when the right cyclin/CdK activity levels are reached does the cycle continue (EK 4.6.A.2). The G2 checkpoint verifies complete DNA replication and repairs; the spindle assembly checkpoint (during M) ensures all chromosomes are properly attached before anaphase. Disruptions to these controls can cause apoptosis or cancer (EK 4.6.B.1). For quick review, study the checkpoints, cyclin–CdK control, p53 and spindle checkpoint in the Topic 4.6 study guide (https://library.fiveable.me/ap-biology/unit-4/cell-cycle/study-guide/4ztGMFvp0v4KAzL65pOP). For broader unit review or more practice problems, see the Unit 4 page (https://library.fiveable.me/ap-biology/unit-4) and practice set (https://library.fiveable.me/practice/ap-biology).