Cell Cycle in Eukaryotes

What is the Hayflick Limit?

There is a limited number of times cells can divide before undergoing replicative cellular senescence.

What are the phases of the Hayflick Limit?

Phase I: Primary culture

Phase II: Period of exponential replication

Phase III: Cell replication ceases but metabolism continues; cells can stay in this state for at least a year before dying.

Why do cells undergo senescence?

Because telomeres cannot be fully replicated each time chromosomes replicate. Once telomeres are gone, cells can no longer replicate.

How many times is a telomere sequence repeated?

100-1000 times at ends of chromosomes.

What happens if telomeres cannot replicate?

Especially problematic for the lagging strand—when RNA primers are removed near telomeres, there's no way to replicate that gap.

Do all cells have telomerase activity?

No, mainly stem cells and germ cells do.

What type of structure is telomerase?

Ribonucleoprotein.

What type of enzyme is telomerase?

RNA-dependent DNA polymerase (reverse transcriptase).

How does telomerase work on the leading strand?

Extends with RNA as a primer.

How does telomerase work on the lagging strand?

Extends with primase and DNA polymerase; still loses some DNA when RNA primer is removed, but telomere length is maintained.

What are the phases of interphase?

G0, G1, S, G2.

What is the longest phase of the cell cycle?

Interphase.

What is mitosis?

Process of nuclear division where a single cell divides into two genetically identical daughter cells. Chromosome numbers do not change.

What is G0?

A phase where quiescent cells can leave the cell cycle, re-enter at G1, or stay permanently (e.g. osteocytes and skeletal muscle cells).

What is the G1 checkpoint?

Checks if DNA is in good enough shape to be replicated.

What is the Intra-S checkpoint?

Prevents stalling/collapsing of replication forks and detects DNA damage.

What is the G2 checkpoint?

Ensures DNA is in good shape after replication and ready to become two daughter cells.

What is the mitotic checkpoint?

Ensures chromosomes are ready to separate into daughter cells.

What is cytokinesis?

Division of cytoplasm after mitosis.

What is the length of the human cell cycle?

24 hours total:

G1: 11 hours

S: 8 hours

G2: 4 hours

M: 1 hour

What is the length of the embryonic cell cycle?

12 hours total, with G1, G2, and M being very short.

Compare human and embryonic cell cycles.

Embryonic cells divide much faster than human cells.

What is Gap 0 (G0)?

Phase when a cell leaves the cell cycle and quits dividing.

What is the correct order of cell cycle phases?

M → G1 → S → G2

What are the players in the G1/S checkpoint?

Cyclins, CDK, p53, p21, Rb

What are CDKs?

Catalytic subunits in heterodimers with cyclins that maintain order during cell division.

What are cyclins?

Regulatory subunits that continuously oscillate due to changes in transcription and degradation.

What CDK does Cyclin D bind with?

CDK 4/6

What phase is Cyclin D active in?

G1

What CDK does Cyclin E bind with?

CDK2

What phase is Cyclin E active in?

G1 to S phase

What CDK does Cyclin A bind with?

CDK1/2

What CDK does Cyclin B bind with?

CDK1

What are tumor suppressor proteins?

Proteins that stop transition into S phase (e.g., Rb, p53, p21).

What is transcription factor E2F?

Regulates expression of DNA replication genes and is critical before initiating DNA replication.

What does DNA polymerase alpha do?

Makes RNA primers for Okazaki fragments and lacks 3'-5' exonuclease activity.

What happens with Rb and E2F in early G1?

Rb binds E2F. CycD/CDK4/6 phosphorylates but not enough to release E2F.

What happens with Rb and E2F in late G1?

CycE/CDK2 further phosphorylates Rb, which releases E2F → binds promoters → starts transcription with RNA Pol II → S phase begins.

What causes oral mucositis?

Radiation therapy and cisplatin damage epithelial cells, leading to apoptosis.

What are the types of DNA base modifications?

Single purine adduct

Intrastrand cross-link

Interstrand cross-link

Single/double strand breaks

What does radiation therapy produce?

Reactive oxygen species (ROS) → DNA damage → replication/transcription interference.

What happens when DNA damage occurs in late G1?

Cell cycle stops to repair DNA → CycE/CDK2 is inhibited with help from p53.

What does p53 do when DNA damage occurs?

Gets phosphorylated, escapes MDM2 inhibition, binds promoters → transcribes p21.

What does p21 do?

Binds CycE/CDK2 → inhibits activity → Rb remains bound to E2F → no S phase → repair or apoptosis.

What happens to Rb after mitosis?

Dephosphorylated by phosphatases → rebinds E2F for next cycle.