Mitosis and meiosis Flashcards
What is the function of mitosis?
- Growth
- Replacement of dead cells
What are the 2 main phases of mitosis?
- Mitotic (M)
- Interphase
What are the phases of interphase?
- 1st gap or growth phase (G1)
- Synthesis (S)
- Second gap or growth phase (G2)
What are the functions of the mitotic and interphase phases?
- Mitotic: true cell division phase
- Interphase: preparation for next cell division event
What is the G0 phase?
- Between M and G1 phases
- Cells are dormant/quiescent
- Not dividing or doing anything else
Which chromosomes are involved in mitosis?
- All chromosomes
- Make 2 homologous copies of each chromosome
Describe what happens in the G1 phase
- First part of interphase
- Normal cell activities
- Increase in cell organells
- Doubling of cell size
Describe what happens in the S phase
- Synthesis
- DNA synthesis
- 2 copies of each chromosome (sister chromatids) are available
- Linked at centromere
- Centrioles replicate
What is the function of the centrioles?
- Part of cytoskeleton apparatus
- Pull chromosome halves to each end
Describe what happens in the G2 phase
- Cell grows in size
- Each cell now has 2 pairs of centrioles
- Mitotic phase starts again
What are the stages within the M phase of mitosis?
- Prophase
- Metaphase
- Anaphase
- Telophase
What happens in prophase?
- Chromatin condenses, distinct chromosomes form
- Each chromosome visible as 2 sister chromatids, joined by centromere
- Nucleolus shrinks and disappears
- Cytoplasmic microtubules of cytoskeleton disassemble then reasseble to form spindle
- One pair of centrioles migrates to each pole of the spindle
- Nuclear membrane disappears
Describe metaphase
- Chromoseoms arrange on equator of spindle
- Homologous chromosomes do not associate
- Ensures daughter cell gets exact copy of parent cell’s DNA
In what phase can we see cell diving in tissue?
Metaphase
Describe anaphase
- Chromatids separate
- Chromatids migrate, led by centromeres, to opposite poles of cell
- Eventually reach poles to make 2 daughter chromosomes
Describe telophase
- Chromosomes unravel
- Nuclear membranes reform
- Nucleoli reform
- Encase in one cell membrane at this point
Describe cytokinesis
- Cleavage furrow forms and deepens until cytoplasm is halved
- Ring of actin filaments attached to inner aspect of cell membrane
Why is there need for control over the cell cycle?
To ensure events are properly times and in correct order
In terms of individual cells, why is it necessary to have control over the cell cycle?
- Damaged DNA must not be replicated
- DNA replication must be complete and just once per cell cycle
- Chromosomes must be positioned on spindle correctly
- Phases of cycle must be synchronous
In terms of the whole animal, why is it necessary to have control over the cell cycle?
- Cell division in tissue/animal coordinated by intercellular signals according to requirements of animal
- E.g. proliferation of lymphocytes in infection or over-proliferation in cancer
What are the 2 levels of control of the cell cycle?
- Intercellular
- Intracellular
What are the points of intracellular control of the cell cycle? What do these require?
- Check points at end of G1, G2 and M phases
- Cyclin dependent protein kinases (Cdks) and cyclins
What is the first checkpoint and what would cause the cell cycle to arrest here?
- G1 to S
- If no mitogenic signal received or if DNA is damaged
- If no mitgenic signal is received but there is no DNA damage, enters G0
What is the second checkpoint and what would cause the cell cycle to arrest here?
- G2 to M
- Arrested if DNA damaged or incompletely duplicated
What is the third checkpoint and what would cause the cell cycle to arrest here?
- M to G1
- Arrested if chromatids are not properly attached to spindle fibres
What happens if the DNA is incorrect?
Apoptosis
Describe Cdks in intracellular control of mitosis
- Cyclin dependent protein kinases
- Activities rise and fall as cell progrgesses through different phases
- Acts as chekpoints
- Cyclical changes in Cdks regulated by cyclins
- Needs to be phosphrylaed to be activated
What does the nature of action of Cdks depend on?
The cyclin protein
What leads to the waves in activity of cyclin through each phase of the cell cycle?
- At start, cyclin genes activated
- Failure of this results in cessation of cycle
- Cyclin proteins destroyed by proteasomes
- Genes encoding cyclins for next cycle are upregulated and expressed
How is Cdks activity regulated?
- Cyclins bind to Cdks (different types of each of these)
- Attachment of ubiquitin molecules to cyclin (bound to the Cdk)
- Once tail of ubiquitin, goes to proteasome complex in cell and protein degraded
Describe the fine regulation of Cdk
- Can phosphorylate active Cdk further
- Makes inactive
- Can switch between active and inactive
- can also control activity through binding of cell cycle inhibitors
What are the extracellular (intercellular) factors that control cell division, growth and apoptosis?
- Mitogens/growth factors (stimulate cell growth)
- Surival factors (inhibit apoptosis and promote cell survival)
What are growth factors?
- Signalling molecules
- Originate from neighbouring cells
What is the function of growth factors?
- Activate pathways which control genes
- Mitogenic
- Maintain correct cell numbers in an organ/system
How do growth factors carry out their function?
- Stimulate cells to enter G1 from G0
- Activate RTKs, Ras and MAPK pathway
- Results in activation of Myc
- Myc increases expression of G1 cyclin kinases: stimulation of DNA synthesis
What signalling cascade do most growh factors use?
MAPK
What is Myc?
Transcription factor
How do abnormal proliferation and DNA damage stimulate cell cycle arrest or apoptosis?
- Excessive Myc activates Arf
- Arf binds to p53 inhibitiory protein Mdm2
- P53 now active, activates p21 and this causes cell cycle arrest or apoptosis
When does apoptosis occur?
- Damaged beyond repair
- Infected with virus
- Undergoing stressful conditions e.g. starvation
Where does the decision for apoptosis come from?
- Cell itself
- Surrounding tissue
- Cells of immune system
Give examples of errors in cell division
- Somatic mutations (damaged cell, make cells cancerous)
- P53 mutation implicated in squamous cell carcinoma
What is meiosis?
A form of nuclear division occuring in germ cells to give rise to mature gametes
What is the product of mitosis?
2 diploid daughter cells with 2 homologous copies of each chromosome
What is the product of meiosis?
4 haploid cells that only carry one copy of each chromosome
What are the 3 major phases of meiosis?
- Meiotic S phase
- Meiosis I
- Meiosis II
What occurs in meiosis I?
Segregation of homologous chromosomes (and crossing over)
What occurs in meiosis II?
Segregation of non-homologous chromosomes (like mitosis)
Describe the first meiotic division in meiosis
- DNA replication
- Consists of interphase and mitotic phase
- Mitotic phase can be divided into prophase I, metaphse I, anaphase I and telophase I
Describe the second meiotic division of meiosis
- No DNA replication
- Consists of prophase II, metaphase II, anaphase II, telophase II
Describe prophase I
- Nucleolus shrinks
- Centrioles migrate to opposite poles
- Spindle forms
- Chromosomes condense
- 5 stages: leptotene, zytogene, paachytene, diplotene, diakenesis
Describe chromosomal condensation in prophase I of meiosis
- Homologous chromosomes undergo synapsis (synaptonemal complex) and lie together to form bivalent structure
- Homologous chromosomes interlink
- Chiasmata form
Describe the leptotene phase of prophase I
Long slender chromosomes visible
Describe the zytogene phase of prophase I
Homologous chromosomes begin to pair up (synapsis)
Describe the pachytene phase of prophase I
- Synapsis complete
- Crossing over occurs forming chiasmata
Describe the diplotene phase of prophase I
- Chromosomes move apart a little
- Each bivalent remains attached at 1 or more chiasmata
Describe the diakenesis phase of prophase I
- Transition to metaphase
- 4 chromatids in each bivalent visible
Describe metaphse I
- Nuclear enveope disappears
- Bivalent chromosomes moe to equator of spindle
- Centromeres of each bivalent chromosome oriente to opposite poles
Describe anaphase I
- Homologous chromosomes separate and migrate to opposite poles of spindle
- One chromosome with 2 chromatids arrives at each pole
Describe telophase I
- Cytoplasmic division starts
- Spindle breaks down
- Nuclear envelope and nucleoli form
Describe prophase II
- Centrioles replicate, migrate to poles
- New spindle forms at right angles to previous one
- Non DNA replication
Decribe metaphase II
- Chromosomes move to equator of spindles
- Chromatids orientate to opposite poles
Describe anaphase II
Chromatids separate and move apart to poles
Describe telophase II
- Spindle disappears
- Nuclear envelope and nucleoli form
- Chromosomes become thread like
What cell type do the spermatogonia and oogonia develop from?
- Primordial germ cells in the gonads
What happens to the spermatogonia at sexual maturity?
- Proliferate by mitosis
- Some remain undifferentiated (spermatogonia stem cells)
- Others differentiate by mitosis
When do the spermatogonia stem cells enter meiosis?
Continually from puberty onwards (influence by androgens)
When does the differentiation to mature sperms occur?
After meiosis is complete
Give a basic overview of spermatogenesis
- primary spermatocytes in testis undergo 1st meiotic division = secondary spermatocytes
- 2nd meiotic division to form spermatids
- Differentiate into spermatozoa
Give a basic overview of oogenesis
- Primary oocyte by first meiotic division to produce secondary oocyte and 1st polar body
- Second meiotic divison = single haploid ovum and second polar body
What are polar bodies?
Packages of chromosomes produced by oogenesis that will not be used any further
Describe the proliferation of oogonia
Proliferate by mitosis inside ovary until enter meiosis
When does meiosis I and II occur in oogonia development
- Meiosis I starts before birth
- Primary oogonia remain in prophase I until puberty
- Resumed at each oestrus cycle to give secondary oocyte
- Arrested at metaphase II
When is meiosis II of oogonia completed?
After fertilisation
What is the importance of exchanging alleles?
- Variation in each generation
- Avoids genetic copies and thus inbreeding
How can genetic reassortment take place?
- Independent assortment of chromosomes
- Recombination (crossing over)
- Mutation
- Segregation of genes (alleles)
- Differences in gene frequency (chance/selection_
Describe the independent assortment of chromosomes in genetic reassortment
- Random orientation of homologous chromosomes at metaphase of meiosis I
- Different possibilities for alignement of homologous chromosomes
- Method of alignment affects outcome
- Increases variation
Describe recombination during crossing over in genetic reassortment
- Recombinant chromosomes carry genes from 2 parents
- also affects linked genes
- Increased by random fertilisation
- Crossing over occurs only between short segments at end of X and Y in sex chromosomes (pseudoautosomal region)
How does random fertilisation increase gneetic variation on top of recombination?
Different gametes carry different combinations which are then rearranged again
Explain gene dosage compensation in females
- Inherit 2 X chromosomes
- One randomly inactivated in embryo
- Only one active copy of X linked genes
How does X chromosome inactivation take place?
- Methylation of DNA
- Expression of antisense transcript (XIST - X-inactive-specific-transcript)
What is the result of X-chromosome inactivation?
- Only one active X in each cell
- Have 2 cell types: half from active X of father, half from active X of mother
- Different alleles present on the X chromosomes reults in mosaic of cells expressing different alleles
Explain dosage compensation and genomic imprinting
- some sections of autosomes inactivated for dosage compensation
- = Genomic imprinting, genes involved are “imprinted genes”
- Due to epigenetic regulation: DNA methylation, non-coding RNA, histone modifications
- imprinted genes are monoallelic expressed (either from maternal or patenral allele)
What are imprinted genes involved in?
- Embryonic growth
- Placental development
- Metabolism
Compare somatic and germ line mutations
- Somatic can cause disease (e.g. cancer) but cannot be passed to next generation
- Germ line are transmitted to future generations
Give an example of germ line chromosomal abnormalities
- Chromosomes remain linked (non-disjunction)
- Can happen at meiosis I or meiosis II
- Leads to abnormal number of chromosomes in germ cells
What is aneuploidy and how does it occur?
- Fertilisation of gametes in which non-disjucntion has occured
- Abnormal number of a particular chromosome
What is a monosomic zygote?
Has one copy of a particular chromosome
What is a trisomic zygote?
Has 3 copies of a particular chromosome
What is polyploidy?
A condition in which an organism has more than 2 complete sets of chromosomes
What are the 4 types of changes that can occur due to breakage of a chromosome
- Deletion removes chromosomal segment
- Duplication repeats a segment
- Inversion reverses a segment within a chromosome
- Translocation moves a segment from one chromosome to a another
Give examples of disorders due to chromosomal defects
- Downs syndrome (aneuploid condition, 3 copies of chromosome 21)
- Klinefelter syndrome
- Tortoiseshell males (XXY)
- Monosomy X, aka Turner syndrome in humans, X0 females who are sterile
