Chromosome segregation

Question 1

How long does mitosis take

Answer 1

About an hour

Question 2

What happens to the chromosomes during mitosis

Answer 2

They are segregated

Question 3

Why is proper chromosome segregation important

Answer 3

Essential for cell proliferation and to avoid an abnormal number of chromosomes in a cell

Question 4

What does aneuploidy mean

Answer 4

An abnormal number of chromosomes

Question 5

What can happen is chromosomes are missegregated

Answer 5

Diseases.
Somatic cells -> cancer
Development -> Downs syndrome

Question 6

How can chromosome missegregation lead to cancer

Answer 6

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

Question 7

What are the stages of a cell cycle

Answer 7

Interphase (G1, S, G2)
Prophase
Prometaphase
Metaphase
Anaphase
Telophase

Question 8

What happens in interphase

Answer 8

Chromosomes and centrosomes duplicate

Question 9

What happens in prophase

Answer 9

Chromosomes start to condense. Centrosomes separate and form asters

Question 10

What happens in prometaphase

Answer 10

Nuclear envelope broken down, microtubules interact with chromosomes

Question 11

What happens in metaphase

Answer 11

Chromosomes bi-orient on spindle and align on the metaphase plate

Question 12

What happens in anaphase

Answer 12

Sister chromatids separate and move towards spindle poles. Spindle poles move apart

Question 13

What happens in telophase

Answer 13

Chromosomes arrive as poles and decondense. Nuclear envelope reassembles.

Question 14

What factors promote mitosis initiation

Answer 14

M-phase cyclin/CDK complex

Question 15

How are M-phase cyclin/CDK complexes regulated

Answer 15

(de)phosphorylation of CDKs

Proteolysis of M-phase cyclins

Question 16

What effect does phosphorylation have on CDKs

Answer 16

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.

Question 17

How are M-phase cyclins regulated

Answer 17

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

Question 18

How do chromosomes become prepared for mitosis

Answer 18

Sister chromatid cohesion established by cohesin complex

Chromosomes are condensed (prophase)

Question 19

Why is the cohesin complex important

Answer 19

Establishes cohesion of sister chromatids.

Enables chromosome bi-orientation, and allows the cell to know which sisters to segregate

Question 20

What subunits are present in the cohesin complex

Answer 20

SMC1/3

SCC1/3

Question 21

How is the mitotic spindle formed

Answer 21

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.

Question 22

How can the length of a microtubule vary

Answer 22

Stabilisation of MT = longer MTs

Destabilisation of MT = shorter MTs

Question 23

How is chromosome motion regulated during meta/ana phase

Answer 23

(De)Polymerisations of kinetochore MTs.

Question 24

When and how are centrosomes duplicated

Answer 24

During S/G2-phase.

Stimulated by S-CDK

Question 25

What is the role of Aurora-B kinase

Answer 25

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

Question 26

What is a syntelic attachment

Answer 26

Mono-orientation of the MTs. No tension. Chromatids cannot separate

Question 27

What is an amphitelic attachment

Answer 27

Bi-orientation of the MTs. Tension. Chromatids can separate

Question 28

How do sister chromatids separate in anaphase

Answer 28

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.

Question 29

How do chromosomes move in anaphase A

Answer 29

Kinetochore MTs shorten due to MT flux and depolymerisation at + end. Movement towards the poles.

Question 30

How do chromosomes move in anaphase B

Answer 30

Move away. Slide between interpolar MTs. Poles pulled towards cell cortex. Movement towards the poles

Question 31

Name some checkpoints in the cell cycle

Answer 31

G1/S - monitors cell size and DNA damage G2/M - monitors DNA replication completion and DNA damage Spindle assembly checkpoint - monitors kinetochore-MT attachment.

Question 32

When does the spindle assembly checkpoint occur

Answer 32

Between metaphase and anaphase. Prevents anaphase onset. Important because anaphase is irreversible.

Question 33

What does the spindle assembly checkpoint consist of

Answer 33

Sensors (kinetochore components) Mediators (MAD/BUB proteins) Effectors (anaphase-promoting complex; APC)

Question 34

How is cytokinesis regulated

Answer 34

Triggered by loss of M-CDK activity Central spindle stabilises cell separation. Both mechanisms ensure cytokinesis only occurs after chromosome segregation

Question 35

How is meiosis different to mitosis

Answer 35

``` Mitosis = DNA replication; Chromosome segregation. Repeat. Meiosis = DNA replication; 2 rounds of chromosome segregation. Repeat. (facilitated by second anaphase) ```