Cell Division And Cycle Flashcards
(19 cards)
Cell fusion- Rao and johnson
Merged cells
S+ G1 = S
G2 + M = M
Discovery of MPF
Cytoplasm from M phase triggers M phase in a G2 cell
Maturation promoting factor
Discovery of cyclin
MPF follows the same peaks as Cyclin B during cycle
Cdc mutants in yeast
Budding yeast mutants
Temperature sensitive for cycle progression
At restricted temperatures were either very long or very short
Concluded Cdc2 is the major controller of G2/M
Maller- purification of MPF
MPF = cdc2/cdk1 (protein kinase) + cyclin B (regulatory)
Activation of MPF
Cyclin B + cdk1 -> inactive MPF
Wee1 phosphorylates Y15
CAK phosphorylates T161
Cdc25 dephosphorylates Y15 -> active MPF
Cdk1 controls G2
What are its substrates
4
Nuclear lamins
Nucleolin
Histones
GM130 (Golgi matrix protein)
In yeast, cdk1 also controls G1
What controls G1/S in mammals and yeast
Yeast- cdk1
Mammal- cdk2 associated with cyclin D and cyclin E
Cdk1 also controls G1 in yeast with cln1,2 and 3
Substrates of cdk2/cyclin D
Transcription factors that regulate the genes of DNA synthesis
Cyclin D and E - regulated by cyclin dependent kinase inhibitors, p21, p27, p15, p16, p19
P53
Gene for li-fraumeni syndrome (high cancer)
Moderate UV exposure repaired by p21
Severe exposure -> death
P27
Monitors cell growth
Induces by external signals and cell to cell contact
P27 knock out mice are larger due to more cells
P27 blocks catalytic site of Cdk preventing ATP binding
P57Kip2
Beckwith Wiedemann syndrome Overgrowth of organs -> cancer Same locus for IGF2 IGF2- knock out mice reduced in size Only one of 2 of the IGF2 parental copies is expressed (father)
DNA damage causes arrest in G2
Rad3+ -> activates Chk1
Chk1 keeps Cdk1 phosphorylated and stops G2->M
In humans this is ATM causing cdc25 to stop G1 -> S
5 phases of cell division
S phase- DNA replication
M phase- cell division (mitosis and cytokinesis)
G1- gap 1 is cell big enough, neighbouring cells
G2- gap 2 is DNA correct
G0- non dividing
ATM definition
Ataxia- staggering gate
Telangiectasia- dilate blood vessel in eye
Mutated
Radiosensitivity and predisposition to cancer
Breast cancer susceptibility genes
BRCA1 and BRCA2
5-10% of Breast cancer
Oncogenesis
Most tumours aneuploid room mitosis
Chromosome segregation error
In meiosis leads to trisomy 21,9,13,18
Role of cdc in chromosome segregation
Free kinetochore- mad2/cdc20 bound
Attached kinetochore- mad2/cdc20 released
Cdc20 activates APC -> esp1 free
Esp1 is a seperase -> chromatids seperate
Inhibition of psd1 (bound to esp1) triggers anaphase as esp1 is then free
Budding yeast mutants unable to seperate sister chromatids
Smc1 + smc3 -> ring that holds DNA Scc1 closes ring Cleavage of Scc1 by Esp1 (determined by APC) Ring opens and releases DNA Chromatids separate