Coding Life: DNA Replication and Cell Division Flashcards
what is cell division required for?
Growth
Cell replacement
Cellular repair
Reproduction
types of cell division
Mitosis
Meiosis
Binary fission
mitosis - what does it, what happens, purpose
Eukaryotes
One cell is copied to produce two identical daughter cells
Growth, cell replacement and repairing
meiosis
Sexual reproduction
One cell is divided into 4 daughter cells, each of which has half the genetic information of the parental cell
Essential for genetic diversity in eukaryotes
binary fission - who, what happens, how does it happen?
Prokaryotes - bacteria and archaea
One parental cell divides to form two genetically identical daughter cells
Prokaryotes are much simpler than eukaryotes - one circular chromosome, no nucleus (nucleoid instead), don’t have to worry about partitioning of organelles
DNA replication occurs at origin of replication (ori) - replication bubble forms at ori and proceeds in opposite directions around the chromosome until it is midway around. Each circular chromosome is attached to the membrane at different sites (initially close but cell elongation moves them apart) so each daughter cell has one chromosome FtsZ protein (highly conserved) accumulates in the cell wall between the attachment sites. This and other proteins form an indent in the cell wall which builds into a partition giving rise to two daughter cells that are genetically identical
prime number and DNA
1’ is closest to nitrogenous base
5’ is closest to phosphate
Phosphodiester bonds form between 3’ OH and the 5’ C
5’ to 3’ because of this
5’ to 3’ on one strand and 3’ to 5’ on the other strand
replication of DNA
Commences at an ori site (multiple ori sites making it more efficient for linear chromosomes)
Two replication forks that travel down the DNA molecule in opposite directions until another ori site is reached (where enzymes act)
Enzyme DNA helicase unwinds DNA to expose individual strands
Topoisomerase relieves tension on DNA molecule by unwinding and repairs any small nicks created
Single stranded binding proteins protect the single stranded DNA from damage
DNA polymerase is responsible for creating daughter strands - new phosphodiester bonds. Uses original DNA strand as a template (semi-conservative replication)
DNA polymerase needs a free 3’ OH in order to add the first nucleotide (made available with an RNA primer made available by RNA primase)
limitations of DNA polymerase
Can only read and synthesise DNA molecules not RNA
Can only synthesis DNA 5’ to 3’
Can only read the template 3’ to 5’
leading vs lagging strand synthesis
Two strands being synthesised at once
Leading strand - reading template 3’ to 5’ so synthesis occurs 5’ to 3’ (same direction as replication fork is travelling). Daughter strand can be synthesised continuously
Lagging strand - template strand is in the wrong orientation (needs to be read 5’ to 3’ which cannot happen) so RNA primase must make several RNA primers short distances apart and the DNA polymerase jumps ahead and synthesises DNA which leads to the formation of short DNA segments called Okazaki fragments which need to be joined by DNA ligase
Leading and lagging continue for the entire chromosome
Due to being linear, leading strand synthesis can go right to the end of the chromosome but lagging strands run out of chromosome for RNA primer to bind to - chromosomes would shorten with every replication
Short, repeating units at the end called telomeres deal with this (made by telomerase) which ensure there is enough DNA at the end for a primer to be synthesised
proof reading capability of DNA polymerase
DNA polymerase only makes mistakes 1 every 100 million nucleotides
Reverses and then removed the wrong nucleotide and replaces it
what does the cell cycle of eukaryotic cells do?
Regulates cell division
Uncontrolled cell division can cause things like cancer (mutations in genes that control cell division)
M phase
Mitosis and cytokinesis
When the parent cell divides into two daughter cells
Chromosomes condense and become more visible
PMAT
interphase
time between two successive M phases 10-14 hours Prepares for cell division Replication of DNA in nucleus Increase of cell size Under a microscope you cannot see the chromosomes in this phase because they are all long and stringy
G1 phase
Gap 1
Size and protein content increase
Regulatory proteins are made and activated
S phase
Synthesis
DNA in nucleus is replicated
Makes sister chromatids (held together by a centromere)
G2 phase
Prepares for mitosis and cytokinesis
Produces spindle fibres and enzymes that segregate chromatids and producing more cellular membrane
G0 phase
No active preparation
Present in cells that do not actively divide
eukaryotic DNa organisation
DNA is organised with histones and other proteins into chromatin and packaged as chromosomes
karyotype
portrait of all the chromosomes
Most human cells have 46 chromosomes
Pairs of homologous chromosomes - genes one from each parent
Sex chromosomes xx and xy
cyclins
Proteins that regulate progression through phases
Many different types often characterised by when they act such as G1/S or S or G2/M or M (even more classes under this)
Bind to CDK (Cyclin Dependant Kinases) which is an enzyme
CDK phosphorylates target proteins (that encode proteins responsible for DNA replication, production of more membrane etc.)
CDK is activated and can then modify its targets by adding a phosphoryl group
Cyclins and CDK complexes are specific usually for each stage of the cell cycle - “gatekeepers” of the cell cycle
Cyclins respond to interactions with other proteins - target proteins mediate transition to next phase
Inhibitors may bind to cyclin CDK complexes and stop their function eg. P53 is a protein that deactivates cyclins when an error has occurred in the DNA. Binds to DNA and produces an inhibitor which blocks the CDK cyclin complex from continuing the cycle. So it no longer goes from G1 to S with the damaged DNA template (daughter cells would have damaged DNA). Cell then goes in G0 - repair DNA or be destroyed
what happens if cyclins don’t work
Depends on what the cyclin/CDK complexes are supposed to do
Many common diseases are due to the complex not functioning properly
No regulation in some areas - might move onto next stage before prepared leading to errors in DNA etc. or the cell won’t go into the next stage at all
what are the classes of cyclins?
G1/S:
D class
S:
E
G2/M:
A
M:
C or B
mitosis - what cells?
Eukaryotes
Also Asexual reproduction in unicellular organisms
Somatic cells divide
PMAT
prophase
Visible chromosomes because they are condensed in the nucleus
The cells assemble mitotic spindle (made of microtubules) that pull the cell apart into seperate cells
Centrosomes organise microtubules and go to opposite ends
pro metaphase
Nuclear membrane starts to break down
Microtubules grow and shrink and attack to the chromosomes (sister chromatids)
On each side of centromere, there are kinetochores where the spindle fibres join
Pull chromatids apart
metaphase
Chromosomes all align at the centre
anaphase
Sister chromatids seperate and move to opposite poles
telophase
Complete set of chromosomes arrives at the spindle pole
Nuclear envelope reforms
Chromosomes de-condense
End of mitosis
cytokinesis in animals
Division into two cells
Contractile ring made of actin forms at the equator
Cytoplasm is pinched and cell is divided in two
cytokinesis in plants
Cell plate is made between cells (in telophase)
Vesicles fuse to make a new cell wall
meiosis - what cells, what happens in each round?
Happens in germline cells which are diploid and become sex cells or gametes which are haploid (half chromosome number)
Gametes are made by meiotic cell division
Maintains correct chromosome number (ploidy level)
Two rounds of nuclear division (meiosis 1 and 2)
Meiosis 1: homologous chromosomes seperate
Meiosis 2: sister chromatids seperate
result of meiosis
4 daughter cells
Each daughter cell has half the number of chromosomes as the parent
Each daughter cell is genetically unique
meiosis I prophase I
Chromosomes become visible
Microtubules are starting to move to poles
DNA replication is ready
Homologous chromosomes pair with each other and lie side by side (synapsis or gene for gene pairing)
When synapsis is complete each pair of homologous chromosomes forms a bivalent
Each chromosome consists of two sister chromatids (4 stranded structure or bivalent)
Crossing over or DNA recombination occurs - chromosomes exchange DNA (does not happen in mitosis)
Nuclear envelope starts to break down, centrosomes move to opposite ends and spindle fibres appear
Spindles attach at centromeres
metaphase I
Paired chromosomes are moved to the midline by spindles
Align randomly
8 different combinations
anaphase I
Homologous chromosomes are pulled away from each other by spindle fibres
Moved to opposite poles
telophase I
Nuclear envelope reforms around two groups
Chromosomes stay relatively condensed and the membrane does not fully reform
cytokinesis I
Cytoplasm splits
Centrosomes duplicate
prophase II
Chromosomes attach to spindles
Sister chromatids are held by centromeres
metaphase II
Chromosomes are pulled to middle
Not in pairs
anaphase II
Proteins that held sister chromatids together are degraded
Sister chromatids are pulled to opposite sides
telophase II
Nuclear membrane reappears
cytokinesis II
Cells divide Now 4 cells that are haploid Gametes Sperm in males In females 3 die off and 1 becomes the egg
zygote
Sperm and egg fuse
Half of DNA from each parent
Divides by mitosis to form a multicellular organism
genetic variation
Independent assortment
Recombination
Segregation of homologous chromosomes
cyclins and CDKs
Cyclins are signalling molecules that dictate progression
CDK phosphorylates target proteins by breaking down ATP to ADP
CDK is the receptor of cyclins
Concentration of cyclins increases in G1 and eventually it reaches a critical threshold when there are enough to bind to specific G1 CDK (cognate) and then CDK phosphorylates target protein and the target protein (transcription factor) is activated and binds to DNA and regulates transcription and gene expression. Turns some genes on and some off depending on what the cyclin CDK complex is supposed to do such as making proteins needed to DNA replication. Moves on to S phase
Occasionally cell isn’t ready to move on or proteins aren’t good enough for DNA and goes to G0 (G1/S cyclin CDK)
Checks that DNA has no breaks before being copied as well
chromosomal abnormality found
Cells sometimes pretend nothing is wrong and mutations happen
Moves to G0 where it can repair and be successful and continue
If it is unsuccessful and the cell is marked for destruction by apoptosis
if G1/S cyclin/CDK complex was not functional
Major errors could occur during DNA synthesis
chromosome structure
Homologous chromosomes - same genes in same order but might have different alleles
Chromosomes only look like an x after DNA replication
One centromere = one chromosome and x shaped and linear shaped both have a centromere
An x shaped has two sister chromatids which are genetically identical
Kinetochore binds to the centromere
MAD 1/2
Mitotic arrest defect 1 and 2
Regulates metaphase into anaphase transition (functional in mitosis and meiosis)
Checks to make sure chromatids attach to spindle and it their don’t attach it blocks transition
If it doesn’t do it’s job properly aneuploidy can happen
Downs syndrome - nondisjunction of chromosome 21
If ND occurs in Meiosis I, the chance of down syndrome is 50% - two gametes with double number and two with non (non viable, would die)
aneuploidies
A group fo genetic disorders where there is an abnormal number of chromosomes
Occurs in mitosis and meiosis
Typically arises due to ND of homologous chromosomes
ND in mitosis: restricted to somatic cells
ND in meiosis: error in germ line
meiosis numbers
96 sister chromatids
4 haploid daughter cells (23)
Reductional step first
And then equational step second
