M1 L2 Flashcards
3 ways replication is controlled
kinases, licencing/unlicencing and checkpoint proteins
What kinases are involved in controlling replication
DDK
Sld1
S-CDK
DDK
P helicase to activate them
S-CDK
P sdl1 protein which comes in after DDK has been P. Also P polymerase –> MCM10 can then come in
What phase of the cell cycle does licencing/unlicencing occur in
licencing happens in G phase, unlicencing happens in S phase
How is Licencing and unlicening controlled
CDK kinase activity (P) => Cdc6 degraded and downregulated. Cdt1 abd MCM exported from nucleus
Describe Ori sites in yeast and compare to ori sites in higher eukaryotes
- 100-200 bp in yeast, 30-100 bp in eukaryotes
- far apart in eukaryotes
- has an essential AT rich region required for ori function but eukaryotes don’t although ori still needs to be AT rich
What 3 things determine Ori sites
chromatin structure
nucleosome position
transcriptional activity
Events at the replication origin G1 phase
cdc6 comes in to complete ORC. MCM1-7 and cdt1 come in. cdc6 and cdt1 come off
Events at the replication origin S phase
cdc45 and GINs come in to make helicase + pol e to make PIC
MCM10 kickstarts replication
RPA binds ssDNA
Orc leaves and pol a and d come in
cdt1 over expression leads to..
more MCM complexes being able to bind to the DNA - too many copies - tumorigenesis
Examples of diseases caused by mutations in proteins that control replication
- Meier-Gorlin syndrome (mutations in ORC1)
- cdt1 and cdt6 overexpressed in some tumours
what controls licencing and unlicencing
CDK kinase activity and transcriptional regulation