Mitosis and Meisosis Flashcards
Why must rates of cell division and the timings of the cell cycle be carefully regulated?
To maintain cell numbers in a given tissue and maintain tissue size
Prevent formation of tumours
What is the division rate of a proliferating mammalian cell?
One division per 24 hours
Do all cells divide?
No
What are the 4 stages of the cell cycle?
1) M phase - Nuclear division, followed by cytokinesis
2) G1 phase
3) S phase - DNA replication
4) G2 phase
What can happen in G1?
Cells can arrest in G1
Some cells can remain permanently in G1
What are the 5 phases of mitosis?
Describe them
1) Prophase
Condensation of sister chromatids
2) Prometaphase
3) Metaphase
Attachment of chromosomes to the mitotic spindle
4) Anaphase
Separation of sister chromatids
5) Telophase
Where does the mitotic spindle initiate from?
Centrioles
What happens to chromosomes during DNA replication?
The DNA in each chromosome (maternal and paternal) is duplicated to form SISTER CHROMATIDS
Sister chromatids are the segregates into daughter cells, so that each daughter cell receives one copy of each the maternal and paternal chromosome
What is the FISSION YEAST model for the cell cycle?
SP yeast:
- When it divides, the cells stay together and created filaments
- Spends a long time in G2 instead of G1
What is the BUDDING YEAST model for the cell cycle?
SC yeast:
- Give rise to 2 daughter cells, where one is smaller than the other
- Don’t have a G2 phase
Why is yeast an important model in the cell cycle?
Identified major genes involved in the cell cycle
What is the advantage of using yeast as a model for the cell cycle?
1) Rapid division rate (<1 hr)
2) Cell cycle control is HIGHLY conserved (human genes have exactly the same function)
3) Yeast can be grown as haploid or diploid
Why is it hard to study the genes in the cell cycle?
- They are crucial for survival
- If mutate the genes to see what they do, won’t be able to grow and maintain the cells
- Cells will die
What techniques make it possible to study the cell cycle genes?
1) Cells with lethal mutations can be maintained as diploids (KO one copy of the genes)
- When want to study - turn into haploids
2) Temperature sensitive mutations allow growth at permissive temperatures
- Mutations function at lower temperatures
- At high temperatures - protein is inactivated
What genes control the cell cycle?
Cdc genes (cell-division-cycle)
Why is the xenopus a good biochemical model of the cell cycle?
- Easy to collect eggs
- Rapid division rate (30 mins)
- Large size - easier to purify proteins
- Cells produce A LOT of proteins
- Can be manipulated by injection of RNAs or chemicals into the oocyte
Describe the process of ‘cell-free mitosis’
1) Purify cytoplasm from an xenopus oocyte
2) Add ATP and frog sperm
3) Mitosis occurs in the tube (but NO cell division or cytokinesis)
4) Makes more DNA and chromosomes
What did researchers do with the large amount of DNA and chromosomes produces by ‘cell-free mitosis’?
What did this identify?
1) Add antibodies for individual proteins - KO the protein in the sample and see where the cell cycle arrests
2) Remove cytoplasm at different time points and study the changes to the proteins over time
Identified regulatory and checkpoint genes
What are the 3 checkpoints in the cell cycle?
What are the questions asked at each checkpoint?
1) Start
Is the environment favourable?
2) G2/M
Is all the DNA replicated
Is the environment favourable?
3) Metaphase-to-anaphase
Are all the chromosomes attached to the spindle?
Why is the start checkpoint important?
A lot of energy is required for the steps after the start checkpoint - don’t want to waste energy
What are cyclins?
- Proteins which are precisely regulated and expressed in different levels during the cell cycle
- Bind to specific CDKs (cyclin-dependant kinases) to activate and regulate their activity
What do CDKs do?
Phosphorylate many proteins which are specific to certain stages in the cell cycle
How does Wee1 kinase modify CDK activity?
Phosphorylates CDK at a second point - inactivating the kinase activity by changing the shape of the CDK
Where does Wee1 kinase phosphorylate CDKs?
NOT near the kinase domain
How does Cdc25 modify CDK activity?
Removes the inhibitory phosphate added by Wee1 kinase (leaving only one phosphorylation by the kinase domain)
Activates the CDK
How does P27 modify CDK activity?
Binds to the whole cyclin-CDK complex, inactivating it
What is APC and what does it do?
Anaphase-promoting complex
A ubiquitin ligase which regulates entry into anaphase
By adding a poly-ubiquitin to M-cyclin in the M-cyclin/Cdk complex - to label the M-cyclin for degradation
What 3 things does APC ubiquinate?
M-cyclin
S-cyclin
Securin
What is Securin?
A molecule which holds sister chromatids together and allows anaphase to commence
What determines if the cell cycle occurs?
- Favourable extracellular environment
- DNA damage
- Un-replicated DNA
- Chromosomes unattached to the spindle
What is MITOSIS?
Formation of 2 daughter cells, containing the same number and kind of chromosomes as the mother cell
What is MEOSIS?
Formation of 4 daughter cells, each with half the number of chromosomes as the mother - in order to generate genetically different gametes
Which genes aren’t passed onto offspring?
Genes in somatic cells
Which gene are passed onto offspring?
Genes within germ-line cells, which are set aside in the organism
Are gametes diploid or haploid?
Haploid - only one homologue from each chromosome
What is the difference between the steps of mitosis and meosis?
Meosis resembles mitosis, but there are EXTRA steps to segregate the homologous chromosomes
What are homologous chromosomes?
Chromosomes which are similar in length, gene position and centromere location (maternal and paternal chromosomes)
What happens before segregation of the homologues occurs?
- Pairing of the duplicated homologues (maternal and paternal)
- Crossing-over and recombination between the maternal and paternal chromosomes
What is meiosis I?
Crossing over and segregation:
1) Germ cell with a single paternal and maternal chromosome
2) DNA replicated
3) Duplicated homologues pair up - crossing over takes place
4) Homologue pair line up on the spindle
5) Separation of the homologs
What does meiosis I form?
2 haploid cells, with each homolog in a different cell - represented by 2 SISTER CHROMOSOMES
How do the sex chromosomes behave together and why?
Behave as homologues, due to SMALL REGIONS of homology
What is meiosis II?
Resembles mitosis:
1) Separation of the sister chromatids at anaphase II
What does meiosis II form?
4 HAPLOID daughter cells
Each with 1 chromosome (maternal OR paternal)
What is meiotic prophase I?
When the homologues pair up
What is paring of the homologous proteins facilitated by?
Synaptonemal complex as well as DNA base pairing between homologues
When does the synaptogemal complex form and what does it do?
Forms in prophase I to allow the homologous chromosome to line up ready for anaphase (separation)
Facilitates the genetic recombination between maternal and paternal chromosomes
What is a chiasma?
The physical point of contact between the 2 non-sister chromatids of the homologous chromosome (where the crossing-over occurs)
How many times does crossing over occur on a given chromosome?
Many times over the length of any given chromosome
What is nondisjunction?
Gametes with an extra chromosome or lacking a homologue as the result of mistakes during meiosis I
Homologues are not separated - one daughter cell ends up with both the homologues and the other daughter cell lacks a chromosome
What are the gametes called that arise from nondisjunction?
What does this mean?
Aneuploid
Don’t have the right ploidy
What percentage of mammalian gametes are aneuploid?
4% sperm
20% eggs
What is the difference between chromosomes and chromatids?
- The chromosome consists of a single chromatid and is decondensed (long and string-like).
- When DNA is copied in S phase - the chromosome now consists of two sister chromatids
