Week 12 Flashcards
What are the three main kinds of Cdks?
- G1/S
- S
- M
How do cyclins interact with Cdks?
Cyclins associate with the kinase regions. They act as master regulators and control when the kinases are active. Cdk levels don’t change but cyclin levels do.
Function of G1-cyclin
Helps govern activity of G1/S-cyclin
Function of G1/S-cyclin
Helps trigger progression through Start, resulting in a commitment to cell-cycle entry.
Function of S-cyclin
Helps stimulate chromosome duplication
Function of M-cyclin
Helps stimulate entry into mitosis
How is G1-Cdk activated?
G1-CDK is activated by corresponding G1 cyclin, which is regulated by various external factors.
Role of mitogens
Mitogens can serve as external factors that stimulate entry into cell cycle
Proto-oncogenes and examples
Proto-oncogenes are genes that become oncogenes (cancer promoting) when they acquire mutations that make them constitutively active. Examples: Ras GTPase, MAP kinases, and Myc
What causes expression of Myc (a transcriptional factor)?
The MAP kinase cascade creates downstream effects that result in expression of Myc (a transcriptional factor)
What does Myc activate?
Myc activates the expression of the G1 cycle (regulates entry into the cell cycle)
Rb
Named after retinoblastoma, a type of cancer of the eye.
Rb is considered a tumor suppressor because loss of its activity leads to cancer.
E2F
Transcriptional regulator that turns on the expression of many genes, including the G1 cyclin and S-cyclin. Promotes its own expression.
Role of Rb
When there’s no signal, Rb is constitutively bound to E2F. When Rb is phosphorylated and inactivated, this allows E2F to be released from Rb.
If Rb is always active, what effect will this have?
Rb is a tumor suppressor gene. If the protein’s activity is inactivated, E2F will always be active and driving the cell cycle, leading to tumors sometimes
Role of CAK
Cdk-activating kinase (CAK) is always present and phosphorylates Cdk.
Why is CAK not sufficient for M-Cdk activation?
Wee1 kinase adds inhibitory phosphate to Cdk.
How is M-Cdk activated?
Removal of the inhibitory phosphate by Cdc25 phosphatase activates M-Cdk.
What does M-Cdk activate and inhibit?
M-Cdk activates Cdc25 phosphatase and inhibits Wee1 kinase (positive feedback!)
What initiates the metaphase to anaphase transition (degrades S- and M-cyclin)?
APC/C
APC/C
APC/C is an E3 ubiquitin ligase – ubiquitinates its substrates and targets them for degradation via the proteosome. Is partially activated by M-Cdk
Challenges of DNA replication in S phase
- Minimize mutational errors during replication
- Every nucleotide must be copied once and only once.
Origin recognition complex (ORC)
- DNA replication begins at the origins of replication.
- Many origins across the genome.
- Origins are bound with Origin Recognition Complex (ORC).
Role of helicases
To unwind DNA
What forms the PreRC, and what effect does this have?
Pair of Mcm helicases (enzymes that unwind DNA) are loaded onto origins to form a prereplicative complex (PreRC).
PreRC is ‘licensed’ and ready to ‘fire’ in the S phase.
How are Mcm helicases activated?
Via phosphorylation
How are origins inactivated and why?
Via phosphorylation so they cannot be licensed again.
Importance of phosphorylation of the preRC after replication
Phosphorylation of the preRC is critical because it prevents replication from happening more than once (undesirable)
At the end of S phase, what do the chromosomes look like?
At the end of S phase, each replicated chromosome consists of a pair of identical sister chromatids glued together along their length.
Cohesin
Cohesin is a protein complex, made in part of SMCs (Structural Maintenance of Chromosomes).
Role of cohesin complex
Cohesin complex needs to be removed for anaphase to proceed (i.e., separation of the sister chromatids) because it keeps sister chromatids together.
Role of condensin complex
The condensin complex helps package chromosomes during prophase
How are condensin complexes similar to cohesin complexes?
- Both have ring structures.
- The condensin complex (like cohesin) is composed of SMCs (structural maintenance of chromosomes)