10-The spindle assembly point

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How is the M phase broken up?
are prophase, prometaphase, metaphase, anaphase A, anaphase B and telophase
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What are kinetochores?
Kinetochore is a link between plus end of microtubules and DNA and exerts a force on the microtubules to aid their chromosome movement during mitosis at all stages. It also signals what stage of the cell cycle it is at
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What is cohesn?
After replication the two sister chromatids are held together by a multi-protein ring complex called Cohesin, thought to encircle both sister chromatids-complex must be opened to allow sister chromatids to be segregated to opposite spindle poles
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Describe the structure of the cohesin ring complex
contains three key proteins Smc1, Smc3 (which are both long coiled-coil proteins) and Scc1 (also known as the Kleisin subunit). There are a number of other accessory proteins
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When will sister chromatid separation take place?
Attachment of microtubules to the kinetochore and tension applied across the sister chromatid pair are necessary to establish bi-orientation of sister chromatids->Only when all chromosomes have become bi-oriented
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What is separase?
The cleavage of the Scc1 (Kleisin) subunit of the Cohesin complex is catalysed by a specialised protease called Separase. During interphase and early mitosis the Separase enzyme is kept inactive by association to an inhibitor protein called Securin.
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What is securin?
When all pairs of sister chromatids are bi-oriented on the mitotic spindle a multi-subunit E3 ubiquitin ligase called the anaphase promoting complex (APC/C) is activated in conjunction with its activator, Cdc20. This ubiquitinates the Securin molecul
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How does separase/securin activity allow sisters to be separated?
Ubiquitination of securin -> releases Separase to allow it to cleave the Kleisin subunit of Cohesin so that the sisters can be physically separated.
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What is anaphase promoting complex?
responsible for destroying cyclin B at exactly same time it allows activation of separase
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How is the degredation of cyclin B mediated?
mediated by the anaphase promoting complex (APC/C). APC/C activity requires the association to an activating protein known as Cdc20. At metaphase to anaphase transition APC/C polyubiquitinates cyclin B which targets it for destruction by proteasome
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What effect does destruction of Cyclin B have?
inactivates the Cdk1 kinase. Notably, overexpression of a mutant cyclin B with a defective destruction box prevents degradation of cyclin B but also prevents sister chromatid association by blocking Securin ubiquitination.
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What effects does APC^Cdc20 activation have?
1-securing structuion->separase activation->sister chromatid separation->anaphase1. Cyclin destruction, Cdkinactivation->Cdk substrate sephos->chromosome movement to poles->A/spinle elongation->B/spindle disassembly, nuclear assembly->telophase
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Activation of APC/C before all sister chromatids have bi-oriented can cause what?
chromosome mis-segregation during mitosis
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What is a bioriented kinetochore?
one kinetochore associated with microtubules from one pole, and another with the other) the kinetochore will not signal to stop the cell cycle
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What effect does a kinetochore have on a monoattached chromosome?
monoattached chromosome (microtubules attached to 1 chromatid not the other) the kinetochore senses it and signals it  inhibition of metaphase to anaphase transition complex by preventing activation of anaphase promoting complex
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what happens if a chromosome is broekn?
If broken, the attached chromosome will move and the unattached will remain in the middle
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What happens if If a cell carries a mutation in a spindle checkpoint component such as Mad2?
mitotic progression is not inhibited in the presence of benomyl and cell division occurs at the normal rate. The spindle defect in these cells causes severe errors in chromosome segregation, however, so that cells eventually die after forming a micro
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Where do checkpoint proteins accumulate? What happens?
at unattached kinetochores -> the activating subunit of the APC is sequestered-> APC doesn’t have its activating subunit-> glue between sister chromatids keepsthem together
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What happens when When microtubules are not fully attached to kinetochores or sister chromatid pairs are not under tension (I.e. when metaphase plate formation is disturbed) ?
Mad2, BubR1 and Bub3 associates to Cdc20 and prevents it from activating the APC/C. This in turn prevents destruction of Cyclin B and Securin(Securin is not destroyed Separase is not activated so Kleisin subunit is not cleaved so sisters dont separat
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Spindle checkpoint proteins do what?
detect unattached kinetochores
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Other cards in this set

Card 2

Front

What are kinetochores?

Back

Kinetochore is a link between plus end of microtubules and DNA and exerts a force on the microtubules to aid their chromosome movement during mitosis at all stages. It also signals what stage of the cell cycle it is at

Card 3

Front

What is cohesn?

Back

Preview of the front of card 3

Card 4

Front

Describe the structure of the cohesin ring complex

Back

Preview of the front of card 4

Card 5

Front

When will sister chromatid separation take place?

Back

Preview of the front of card 5
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