Cell Replication Flashcards
What are the phases of the cell cycle?
G0
G1
S
G2
M
Which phases take place during interphase state?
G1+S+G2
In which phase does DNA replication occur?
S Phase (interphase)
In which phase does mitosis occur?
M Phase
What is G0 Phase?
Gap, no cell division
What happens at G1 checkpoint?
Checked if environment favours cell replication
What happens at G2 checkpoint?
Checked if all DNA is replicated and no DNA damage is present
What happens at M checkpoint?
Checked if all chromosomes are properly attached to the spindle and ready for cell cleavage
What happens if G2 checkpoint is not passed?
DNA repair or Apoptosis
What stimulates the cells in G0 phase to enter G1 phase?
Growth factors
What is c-Myc?
a transcription factor that stimulates the expression of cell cycle genes (also proto-oncogene)
What is the likely outcome of overexperssion of c-Myc?
Tumour growth
What is Cdk and which cells would have it?
Cyclin dependent kinase found in. proliferating cells
When is Cdk active, what does it do?
Active when cyclin is present, carries out phosphorylation of proteins
Which amino acids are substrates for Cdk and why?
Serine, tyrosine and threonine as they all have hydroxyl groups
Why are cyclins boh produced and degraded at the same time?
Different cyclins with different concentrations at different times to control the cell cycle
Put the molecules in order to make cascade: Cdk 4/6:cyclin D complex, cyclin D, growth factors, c-Myc
What do the checkpoints check for in the cell (generalised)?
What are the advantages of kinase-kinase regulations?
Signal amplification
Diversification
Opportunity for regulation
(reversal by phosphatases)
What are the names of Cdk molecules present in proliferating cells?
Cdk 1, 2, 4, 6
What are the names of cyclins transiently expressed at specific points in the cell cycle?
Cyclin A, B, D, E
How is Cdk activity regulated?
Interaction with cyclins
Phosphorylation
How is a Cdk:cyclin complex activated?
Through phosphorylation and removal of inhibitory phosphate
What kind of feedback does the active Cdk provide?
Positive feedback for activation or inhibiton of kinases
What are the 2 types of cyclins?
S cyclin (for Interphase)
M cyclin (for Mitosis)
What is the degradation mechanism of cyclins?
Ubiquitination/ubiquitylation tags cyclins for degradation in proteasome
What is the order of Cdk:cyclin complexes activated sequntially starting from stimulation by c-Myc?
4/6:D
2:E
2:A
1:B
What is the role of Retinoblastoma (Rb) protein?
Tumour supression - inactivating transcription factors
How is Rb protein inactivated?
Through phosphorylation
What is E2F and how does it contribute to the cell cycle?
E2F is a transcription factor and regulates the expression of several genes need for cell cycle progression - can be inactivated by Rb
What causes DNA damage?
X-rays
What is Rb protein named after?
Eye tumour in children caused by inactive or missing Rb
Which protein is activated in case of DNA damage and how?
p53 is activated through phosphorylation by protein kinase
How does p53 interfere with the cell cycle?
Upregulates production of p21 which inhibits cdk:cyclin complexes
What happens to active p53 in absence of DNA damage?
Degraded in proteasome
Which oncogenes are overly expressed in breast cancer?
EGFR/HER2 and/or Cyclin D1
What does the overexpression of EGFR/HER2 result in?
Breast cancer
What is the treatment for HER2+ metastatic breast cancer?
Herceptin antibodies
What is Ras?
An oncogene - mutationally activated in many cancers (e.g. pancreatic, lung, colorectal, thyroid)
What does the overexpression of Cyclin D1 result in?
Breast cancer
What is the cause of 80% of small cell lung cancers?
loss of function in mutated Rb protein
What is the cause of 50% of all human cancers?
loss of function in mutated p53
