White Lecture 4 "Cell cycle 2" Flashcards
Describe condensin
five subunit protein complex
related to cohesin; protein that holds sister chromatids together
2 SMC subunits and 3 Non-SMC subunits
forms a ring like structure and uses ATP to promote compaction and resolution of sister chromatids
What is the 2 step process that avoids the chromatids being broken when they are being pulled apart
- chromosome condensation and resolution
Define resolution
sister chromatids become distinct separate units
Describe the mitotic spindle
bipolar array of microtubule proteins
pulls sister chromatids apart at anaphase
M-CDK triggers the assembly
Describe tubulin
heterodimer of alpha and beta tubulin with non-covalent bonds
What is the plus end of the microtubule?
The fast growing end
What is the minus end of the microtubule?
The slow growing end
What are the 3 types of microtubules?
- kinetochore
- interpolar microtubules
- astral microtubules
Define kinetochore microtubules
attach each chromosome to the spindle pole
Define the inter polar microtubules
Hold two halves of the spindle together
Define astral microtubules
Interact with the cell cortex
What does the plus end of the kinetochore tubules attach to?
attach to the sister chromatid pairs at large protein structures called kinetochores and to the centrosome
What does the plus end of the inter polar microtubules attach to?
The plus end of one pole interacts with the plus end of the other
Describe the astral microtubules in the cell
radiate outward from the poles and contact the cell cortex helping to position the spindle in the cell
Define the MTOC
Where all the microtubules are nucleated from;
microtubules grow outward from the MTOC from the plus end
What is the gamma tubulin ring complex
responsible for the nucleation of the microtubule growth
What is the function of gamma turc
binds to the negative end and elongates the microtubules
Describe centrioles
protein organelles called a centrosome
consists of a matrix and a pair of centrioles
contains gamma turc
What are the two types of motor proteins?
Dyneins and kinesins
Describe dyneins
tends to move toward the center of the cell
minus end is directed to the microtubule motor
Describe kinesisns
tend to move toward the periphery
walks toward the positive end of microtubules
has 2 globular heads and elongated coil coil tails
plays an important role in chromosome separation
What is dependent on the motor proteins?
assembly and function of the mitotic spindle
What are the 4 major proteins that are involved in the spindle assembly and function?
- kinesin-5
- kinesin- 14
- kinesin- 4, 10
- dynein
Describe kinesin-5
- made up of two motor proteins that interact with the plus end of the anti-parallel microtubule
- move two anti-parallel microtubules past each other to force the spindle poles apart
- moves towards the plus end and forces the chromosomes apart
Describe Kinesin-14
- minus oriented directed motor with a single motor domain
- move toward the minus end and pulls the poles together
What happens if there is not kinesis-5 present in the cell
the spindle collapses
Describe kinesin-4,10
also called chromokinesins
move toward the plus end
push attached chromosomes away from the pole
How are the chromosomes brought back to the centrosome?
via the push pull motion’ the kinesin 4, 10 pushes toward the plus end of the inter polar or astral microtubule and the kinetochore microtubules pulls it back
Describe dyneins
minus end directed motors
links the plus ends of the astral microtubules to the actin skeleton at the cell cortex
moves toward the minus end of the microtubule, the dynein motors pull the spindle poles away from each other
Describe kinetochores
giant multi-layered protein structure that is built on the chromosome
allows for attachment of the spindle to the chromosomes
has multiple microtubules attached to it
Describe the exposed end of the kinetochore
there is an exposed open end that allows for the addition and removal of tubulin subunits
Describe the binding of the kinetochore
- bipolar attachment
- attach the kinetochore to the microtubule on the opposite side of the chromosome
- sister chromosomes attach to opposite poles of the spindle
How is stable attachment detected by the kinetochore?
Tension
What are the 3 forces that are involved in chromosome movement
- depolymerization
- microtubule flux
- polar ejection force
describe depolymerization
major force pulls the kinetochore and the chromosome toward the spindle
depolymerization of the plus end of the microtubule pulls the kinetochore poleward
Describe microtubule flux
microtubules move towards the spindle pores while being dismantled at the minus ends
tubulin is added at the plus end while being removed at the minus
ESCALATOR
Describe the polar ejection force
kinesin-4, 1o motors on the chromosomes interact with microtubules and transport chromosomes from the poles
push pull phenomenon
What are the final steps of mitosis?
spindle is prepared organization sister chromatids separate m-cdk activates APC/C cohesin system
Describe anaphase A
chromosomes move apart due to the depolymerization at the kinetochore
Describe anaphase B
The separation of spindle poles themselves by kinesin-5 motor proteins
Describe cytokinesis
final step of the cell cycle
at the end of anaphase
What are the 4 stages of cytokinesis?
- initiation
- contraction
- membrane insertion
- completion
Describe the contractile ring
causes the cleavage furrow and is made up of actin and myosin
formin helps in the formation of the ring as it is making the actin
What are the class 1 extracellular signaling molecules?
mitogens- stimulate cell division by triggering G1/S-cdk activity
Describe the Class 2 extracellular signaling molecules
growth factors
Describe the class 3 extracellular signaling molecules
survival factors suppress form of programmed cell death known as apoptosis
What happens if just one of the classes of the extracellular signaling molecules that is involved in controlling cell division is missing?
CANCER
Describe mitogens
act when more cells are needed
Describe the action of the mitogens
- mitogen binds to the receptor
- Ras causes activation of the MAP kinase cascade
- leads to the increase of gene regulatory proteins including Myc
- Myc promotes entry into cell cycle by increasing the expression of G1 cyclins and get active G1 Cdk-Cyclin
What does the G1-Cdk-cyclin activate and describe what happens after that
E2F proteins are activated
binds to the promotes of the G1/S cyclin and the S cyclin genes –> transcription
enter the S phase of the cell cycle
DNA synthesis begin
What is the function of the Rb protein? And what does this action cause?
Inhibits E2F which shuts down the entry into the S phase of the cell cycle
Rb is a tumor supressor
What happens if the Rb protein is not working?
There is not control and therefore CANCER can occur
Describe retinoblastoma protein family
Loss of copies of the Rb genes which leads to cell and tumor proliferation of the retina;
Which protein kinases are activated if there is DNA damage?
ATM and ATR protein kinases
What do the ATM and ATR genes do when the damaged DNA is detected?
phosphorylate Chk1 and Chk2 proteins
What is the major target of the Chk1 and Chk2 proteins?
p53 protein which stimulates the p21
Describe ataxia telangiectasia
ATM protein is defective; autosomal recessive; no DNA repair
In what percentage of cancers is Ras mutated?
30%
In what percentage of cancers is p53 mutated in?
50%
Describe the PI-3 kinase pathway
adds ATP to inositol phospholipids
activates TOR which activates factors for cell growth
What are the three mechanisms that coordinate cell growth?
- Rate of cell division is determined by extracellular factor
- cell growth and division is controlled by growth factors and mitogens
- cell growth and division both stimulated by extracellular factor
What does myostatin do?
inhibits cell growth
