mitosis Flashcards

1
Q

whats the overall issue in mitosis

A

-In order to divide properly its no good just replicating your DNA
-The cell has to be able to separate long pieces of DNA without breakage, or tangling (which could lead to too many chromosomes ending up in one daughter cell
-The cell has to rearrange the DNA into short, condensed chromosomes
-These are then pulled apart in ANAPHASE

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2
Q

what are the two phases in mitosis

A

-Chromosome condensation
-Sister-chromatid resolution

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3
Q

what are chromosomes

A

linear DNA molecule

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4
Q

whats a centromere

A

-Region where the spindle attaches

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5
Q

whats homologous chromosomes

A

-Have the ‘same’ genes arranged in the same order
-1 Inherited from father, 1 from mother

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6
Q

what are chromatids

A

-the newly copied DNA strands still joined to each other by a centromere

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7
Q

what happens in M phase

A

-Prophase – condensation of sister chromatids (identical copies).
-Metaphase – attachment of the mitotic spindle to the kinetochore by microtubules.
-Anaphase – separation of sister chromatids to opposite poles.
-Telophase – nuclear envelope reassembly, start of cytokinesis

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8
Q

what happens to cyclin levels in mitosis

A

-collapse in cyclin levels due to change from metaphase to anaphase

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9
Q

what do cyclin dependent kinases do

A

-activate genes and turn on proteins

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10
Q

whats the M-Cdk trigger when M-Cdk drives entry into mitosis

A

-Assembly of the mitotic spindle
-Each sister chromatid is attached to an opposite pole
-Chromosome condensation
-Breakdown of the nuclear envelope
-Rearrangement of the actin cytoskeleton + Golgi

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11
Q

how does M-cyclin and Cdk trigger entry into mitosis

A

-Cdk1 (like as) m-cyclin (like substrate)
-M-cyclin levels increase through G2 and M (by increase in Cyclin B expression) to create a pool of inactive M-Cdk complex.
-in late G2 the Cdc25 phosphatase is triggered to activate a positive feedback loop rapidly activating mitosis.

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12
Q

what causes Cdc25 to activated

A

-Possibly S-Cdk complexes
-Once started +ve feedback will inhibit Wee1 and activate more Cdc25

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13
Q

whats APC

A

-Anaphase-Promoting Complex
-in Metaphase – attachment of the mitotic spindle to the kinetochore by microtubules.
-in Anaphase – separation of sister chromatids to opposite poles.
-Progression trough metaphase/anaphase transition -> driven by protein destruction
-Contrast this to phosphorylation which used activate/inhibit proteins such as M-cdk

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14
Q

what are the 2 targets when APC is a ubiquitin ligase

A

-(1) S+M cyclins: if these are destroyed most CDKs are inactivated -> CDK targets are Dephosphorylated (by phosphatases)
-APC/C kept on in early G1-> turned off as G1/S-CDK activated to allow Cyclin accumulation
-(2) Securin (part of the system which protects protein linkages which holds proteins together: protects the protein linkages that hold sister chromatids together
-Destruction -> activates a protease that separates the sister chromatids ->anaphase

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15
Q

What can go wrong in mitosis

A

-2-hit hypothesis. Most genes need mutations on BOTH alleles to cause a phenotypic change.
-In the case of a tumour-supressor gene it would be any mutations that lead to inactivation of the proteins function. Eg Rb
-We call this change a Loss-of-heterozygosity
-It can be by several mechanisms – it doesn’t matter
-You can also get the loss of the allele – ie hemizygosity – so in effect you have one copy, if this is mutant then you may have a problem

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16
Q

whats chromosome non-disjunction

A

-The most obvious error is chromosomes ending up in the wrong daughter cell
-eg lagging chromosomes during anaphase

17
Q

whats the Basic Structure of the Mitotic spindle

A

-Interpolar Microtubules: Overlap- can slide over one another
-Kinetocore Microtubules: attach to chromosomes at kinetochores (at centromeres)- link spindle pole to chromosome
-Astral Microtubules: Contact cell cortex to position the spindle
-Centrosome: centriole surrounded by pericentriolar matrix. This act to nucleate microtubules

18
Q

How are inappropriate attachments sensed?

19
Q

what are the correct attachments

A

-Kinetocores pulled in opposite directions

20
Q

what are the incorrect attachments

A

-Tension is lower-> inhibitory signal -> loosens the microtubule attachment site

21
Q

what does The activation of APC/C by Cdc20 lead to

A

-ubiquitylation and destruction of securin
-Cdks can phosphorylate separase-> inhibition
-BUT:
=in anaphase -> cyclins destroyed
=>Cdk inactivation-> less separase phosphorylation -> activation

22
Q

what are the two types of anaphase

A

-A and B
-ANAPHASE A: kinetochore microtubules separate by shortening, then chromosomes pulled to different poles
-In ANAPHASE B the ASTRAL microtubules pull the cells apart by motors and depolymerisation. The interpolar microtubules slide past each other
-It is in TELOPHASE that the nucleus (nuclear membrane etc) is reassembled and cytokinesis can begin

23
Q

whats hemizygosity

A

-where you are left with the mutant allele, you effectively have inactivated a protein as no active protein can be made

24
Q

what is the reason for exchange in genetic material

A

-in G2 and M phase, chances of breakage is possible and there are repairs which causes exchange of genetic material
1)S-phase Chromosome replication
2)G2, M Mitotic recombination
3)End of Mitosis Chromatid segregation

25
Q

LOH by gene conversion

A

-DNA polymerase begins replication on template strand of chromosome B
-DNA polymerase jumps to template strand of chromosome A (homologous)
-DNA polymerase copies some of A then jumps back to template strand of chromosome B

26
Q

what are the 3 reason mitosis can go wrong inducing LOH

A
  • Non-disjunction
  • Mitotic recombination
  • Gene conversion