Chromosome separation Flashcards
What phase of mitosis involves chromosome segregation?
The M phase (1hr) involving division and cytokinesis
Needed or cell proliferaion
Avoids an abnormal number of chromosomes in the daughter cell and DISEASE
What is aneuploidy?
Avoids an abnormal number of chromosomes in the daughter cell.
What are the consequences of mis-segregation?
Cancer (somatic cells)
If duplication is correct but functional genes arent separated; unfunctional genes may not be segregated to the same cell as functional supressor genes and so links to cancer (uncontrolled)
Down syndrom
MITOSIS OVERVIEW
1) Interphase (G1, S, G2) duplication
2) Prophase- condensing, asters
3) Prometaphase- nuclear envelop broken down, microtubules
4) Metaphase, orientation of chromosomes, align on M plate
5) Anaphase- sister chromatids separate, spindles
6) Telophase- chromosomes arrive at poles and decondense
What promotes mitosis? And how is it regulated?
M-phase cyclin (CDK)
1) Regulated by the phosphorylation of CDKs; through 2 positive feedbacks
2) by PROTEOLYSIS of M-cyclins
How do chromosomes become prepared for mitosis?
1) Sister chrom. COHESION made by COHESIN COMPLEX in S phase; this holds the sister chromatids together.
COHESIN COMPLEX:Smc3, Smc1 (hinge) + Scc3, scc1
It is needed for ORIENTATION and where to segregate to.
2) Chromosomes are condensed in prophase; cohesins are REMOVED, and condensin complexes are used to keep 2 loops of DNA of the same chromatid together
Mitotic spindle classes
1) ASTRAL (in all directions, orientation)
2) Kinetochore microtubules (chromosome motion)
3) INTERPOLAR MTs generate the FORCES FOR SEPARATION
MTs =tubulin heterdimers- protofilaments that constantly grow and shrink via GTP hydrolysis
Microtubule instability
1) MAPS (mt ass. proteins) stabilise tubule
2) catastrophe factor (kinesin) destabilises
Chromosome motion in metaphase and anaphase
Role of motors
kinesin bridges interpolar mt/ length of spindle
some kinesins push chromosome onto plate
Dynein pulls astral mts on cell cortex; focuses mt
MTOC
the y-tubulincomplex gives nucleation site (like pores on the structure surface which the extending mt a distal plus end protrude out of.
Duplicating the centrosome in S/G2
CDK stimulated to promote elongation of daughter centriole in S
Prophase shows centrosome separation followed by a mitotic spindle between two centrosomes
Site of MT attachment
Kinetochore with a plate like structure; one kineochore on one chromatid, but he kinetochore can be attached to 30 MT via a Ndk80/HEC1 complex.
i) kinetochore capture by MT
ii) MT dependent kinetochore transport towards spindle
iii) sister kinetochores on chromatids interact with MTand are reorientated. (biorientation)
Biorienation (both sisters have one kinetochore needed for no error segregation)
What is Aurora-B kinase
phosphorylates kinetochores components when uncorrect biorientation (two MT on one KT and so not tenion
KT delocalise and Dephosphorylate from kinase
Anaphase- sister chromatids separate from eachother
i) M-CDK - mitoticspindle
ii) active separase cleaves cohesions, allowing sisters to be be pulled
securin-separase complex is broken down by active APC/C (complex of APC/C and cdc20)
What triggers cytokinesis?
1) Loss of M-CDK activity.
i) contractile ring formed (actin and myosin)
2) ii) central spindle (interpolar MT) stabilises advancing cleavage furrow
2 MECHANISMS HERE
