Flashcards in Chromosome segregation Deck (35):
How long does mitosis take
About an hour
What happens to the chromosomes during mitosis
They are segregated
Why is proper chromosome segregation important
Essential for cell proliferation and to avoid an abnormal number of chromosomes in a cell
What does aneuploidy mean
An abnormal number of chromosomes
What can happen is chromosomes are missegregated
Somatic cells -> cancer
Development -> Downs syndrome
How can chromosome missegregation lead to cancer
A cell may have two types of tumour suppressor gene (1 active/ 1 inactive). If a cell missegregates and doesnt have an active tumour suppressor gene -> cancer
What are the stages of a cell cycle
Interphase (G1, S, G2)
What happens in interphase
Chromosomes and centrosomes duplicate
What happens in prophase
Chromosomes start to condense. Centrosomes separate and form asters
What happens in prometaphase
Nuclear envelope broken down, microtubules interact with chromosomes
What happens in metaphase
Chromosomes bi-orient on spindle and align on the metaphase plate
What happens in anaphase
Sister chromatids separate and move towards spindle poles. Spindle poles move apart
What happens in telophase
Chromosomes arrive as poles and decondense. Nuclear envelope reassembles.
What factors promote mitosis initiation
M-phase cyclin/CDK complex
How are M-phase cyclin/CDK complexes regulated
(de)phosphorylation of CDKs
Proteolysis of M-phase cyclins
What effect does phosphorylation have on CDKs
Inactive when phosphorylated.
Wee1 -> CDK-inhibitory kinase.
CDC25 -> phosphatase that is activated by the M-phase cyclin/CDK complex. Removed a phosphate and activates CDK.
How are M-phase cyclins regulated
APC/C (anaphase-promoting complex/cyclosome) is activated by forming a complex with CDC20 or CDH1. When active it can target M-cyclin for ubiquitin degradations
How do chromosomes become prepared for mitosis
Sister chromatid cohesion established by cohesin complex
Chromosomes are condensed (prophase)
Why is the cohesin complex important
Establishes cohesion of sister chromatids.
Enables chromosome bi-orientation, and allows the cell to know which sisters to segregate
What subunits are present in the cohesin complex
How is the mitotic spindle formed
Astral MTs radiate from centrosomes and orient the spindle
Kinetochore MTs attach to kinetochores and regulate chromosome motion
Interpolar (polar) MTs inter-digitate at spindle equator and generate force to separate the poles.
How can the length of a microtubule vary
Stabilisation of MT = longer MTs
Destabilisation of MT = shorter MTs
How is chromosome motion regulated during meta/ana phase
(De)Polymerisations of kinetochore MTs.
When and how are centrosomes duplicated
Stimulated by S-CDK
What is the role of Aurora-B kinase
Important for error correction in mitosis.
If the sister chromatids are not separated correctly, then the MT components are phosphorylated (by Aurora-B kinase)and cannot separate the chromatids.
When the right tension is applied, Aurora B is inactivated/delocalised. MT components are dephosphorylated and the chromatids can separate
What is a syntelic attachment
Mono-orientation of the MTs. No tension. Chromatids cannot separate
What is an amphitelic attachment
Bi-orientation of the MTs. Tension. Chromatids can separate
How do sister chromatids separate in anaphase
Separase usually inactive (by securin). Active ACP/C is able to ubiquitinate securin and signal for degradation.
Active separase breaks the bond between SCC1/3 in the cohesin complex. Chromatids are free to separate.
How do chromosomes move in anaphase A
Kinetochore MTs shorten due to MT flux and depolymerisation at + end.
Movement towards the poles.
How do chromosomes move in anaphase B
Move away. Slide between interpolar MTs. Poles pulled towards cell cortex.
Movement towards the poles
Name some checkpoints in the cell cycle
G1/S - monitors cell size and DNA damage
G2/M - monitors DNA replication completion and DNA damage
Spindle assembly checkpoint - monitors kinetochore-MT attachment.
When does the spindle assembly checkpoint occur
Between metaphase and anaphase.
Prevents anaphase onset.
Important because anaphase is irreversible.
What does the spindle assembly checkpoint consist of
Sensors (kinetochore components)
Mediators (MAD/BUB proteins)
Effectors (anaphase-promoting complex; APC)
How is cytokinesis regulated
Triggered by loss of M-CDK activity
Central spindle stabilises cell separation.
Both mechanisms ensure cytokinesis only occurs after chromosome segregation