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CELLS – how it all comes together I


DNA is in nucleus of cell in ‘chromosomes’
DNA is an α helix strand & is supercoiled into
‘packages’ = chromosomes
Humans = 23 chromosome pairs (46 total)
22 autosomes + 2 sex chromosomes

Cells have a lifecycle → cell cycle – part of this


cycle involves replication.
Cell cycle checkpoint
(G2/M) Cells must divide!
Cycle can Holt here if If a somatic cell → mitosis (to replicate)
DNA damage found If a germ cell → meiosis (to form gametes)

CELLS – how it all comes together II

Cells have a lifecycle (cell cycle_ – part of this


cycle involves duplicating

Cells must divide!


If a somatic cell → mitosis (to replicate)
If a germ cell → meiosis (to form gametes)

FYI!!
‘CHROMATID’ is actually one copy of all the DNA on
a chromosome eg chromosome 1 – these are what
exist in a cell in between divisions. The familiar cross
looking chromosome is actually what DNA looks like
after it’s replicated ie the cross is made of two
chromatids, one copy of the other. Be careful, as the
term ‘chromosome’ is often used for both.

Cell cycle checkpoint (G1/S)


CELL CYCLE P53 or Rb (retinoblastoma
product) can holt cycle here if
DNA damage found
INTERPHASE
• Cell between divisions –
chromosomes NOT visible
by LM
Consists of three phases:
G1 Phase
• Growth. Metabolism,
preparation for division

S Phase
• DNA replication: chromatids
become chromosomes

G2 Phase
• As G1 – prepare for Mitosis

PROPHASE
• Chromosomes condense
• Nuclear membrane
disappears
• Spindle fibers appear &
attach

METAPHASE
• Centromeres of chromatid
pairs line up along
metaplate of cell (equator)

ANAPHASE
• Centromeres divide &
chromatids (one from each
pair) move to opposite
poles of cell

TELOPHASE
• Nuclear envelope
reappears
• Chromosomes
uncondensed (chromatin)
• Spindles break up

CYTOKINESIS
FYI!! • Cytoplasmic division
Sometimes • Cleavage furrow forms &
intermediate progresses inwards
phases are separating cytoplasm into
also two
considered …
eg
‘prometaphase’
as illustrated to
left.

REDUCTION DIVISION (Meiosis I)
PROPHASE 1
- Chromosomes condense
- Nuclear envelope disappear
- Chromosomes arrange in
homologous pairs
- Crossing over occurs now
METAPHASE 1
- Homologous pairs line up on the
equator
ANAPHASE 1
- members of homologous pairs
separate with one member moving
to each end
- centromeres do not split
TELOPHASE 1
- cells now haploid cf original
- nuclear envelope reappears
- chromosomes decondense
- CYTOKINESIS

REDUCTION DIVISION (Meiosis II)


Basically the same as Meiosis I
PROPHASE I
- Chromosomes condense
- Nuclear envelope disappear
- Chromosomes arrange in
homologous pairs
METAPHASE II
- Homologous pairs line up on the
equator
ANAPHASE II
- members of homologous pairs
separate with one member moving
to each end
- centromeres do not split
TELOPHASE II
- cells now haploid cf original
- nuclear envelope reappears
- chromosomes decondense
- CYTOKINESIS

Final product:
4 haploid cells all genetically different
DEFINITION!!
Nucleoside: base + sugar
Nucleotide: base + sugar +
phosphate
DNA Repllication
- Begins when specialized enzymes “unzip” DNA double helix.
- As the two strands separate, purine & pyrimidine bases on
each strand are exposed & are ‘sticky’, hence attract their
complementary bases (as free nucleosides & nucleotides)
from within nucleus. One strand runs in a 3’-5’ direction, and
the other in the opposite direction
- The original strand of DNA with ‘sticky ends’ directs the
synthesis of a new strand of DNA through complementary
base pairing. DNA polymerase enzyme joins all the
nucleotide components to one another.
- Old strand then unites with new strand to reform a double
helix.
DNA polymerase joins nucleotides in a 5′end-3′end direction
therefore can run along one strand (leading strand) easily. However,
the other strand requires it to run in the opposite direction. Therefore,
the 3′-5′ strand (lagging strand), is synthesized in short segments in
the correct 5′-3′ direction. These short segments placed on the
lagging strand are Okazaki fragments & are ultimately joined
together by the enzyme DNA ligase to form the new DNA strand.
See picture below
OVERVIEW

2 PROCESS:

TRANSCRIPTION
Relevant part of DNA ‘unzipped’ & transcribed to
mRNA which is single stranded & moves out
into cytosol to Ribosomes.

TRANSLATION
mRNA feeds through Ribsome which ‘reads’ in
groups of three (codons) & translates to tRNA
which goes and fetches the corresponding
amino acid as determined by the genetic code
(see wheel). Ribosome then connects each
amino acid to the chain to create the protein
encoded by the gene.
TRANSCRIPTION

TRANSLATION
Single base substitutions
A single nucleotide base becomes replaced by another. These single base changes are also called point
mutations. If a purine (a, t→ purine or a pyrimidine (c, g) → pyrimidine = transition. If a purine → pyrimidine or
vice-versa = transversion.

MISSENSE MUTATIONS
- New base alters a codon resulting in a different amino acid
being incorporated into the protein.
- Eg Sickle Cell Anaemia: 17th nucleotide in gene for β chain
of Hb changes from A→T = codon GAG→GGT = sixth aa
changes from Glu→Val altering quaternary structure of Hb =
pathology!

NONSENSE MUTATIONS
- New base changes a codon from coding for an aa to a stop
codon which causes translation of mRNA to stop
prematurely = truncated protein → unlikely to function
- Occur in 15-30% of all inherited diseases incl. CF,
Haemophilia, DMD

SILENT MUTATIONS
- Substitution of a base which causes no change in the aa &
∴ the final protein
- Can uccur because numerous codons encode the same aa.
- Only detectable by sequencing the gene

SPLICE SITE MUTATIONS


- Introns must be spliced out from mRNA to produce correct protein & must be very accurate
- Guided by nucleotide signals at the splice sites
- If a mutation alters these, the intron may not be removed = incorrect protein produced

INSERTIONS AND DELETIONS


- Extra base pairs (from a few to thousands)
may be added or deleted for DNA of a gene
- Insertions & deletions of one or two bases or
multiples of one or two cause
FRAMESHIFTS (shift in the reading frame of
the triplet codons) = can be devastating &
protein may be useless
- Insertions or deletions of 3 or multiples of 3
may be less serious as they preserve the
open reading frame
- Eg Huntingtons Disease or fragile X
syndrome both trinucleotide repeat diseases where a triplet is repeated

CHROMOSOMAL MUTATIONS
- Any change in the structure or arrangement of the chromosomes
- Occur more frequently in the crossing over stage of meiosis
TRANSLOCATIONS

- the transfer of a piece of one chromosome to a non-


homologous chromosome
- They are often reciprocal, with the two chromosomes
swapping segments with each other
- Eg Philadelphia Chromosome in CML between Chr 9
and 22 = abnormal hybrid gene (bcr-abl) = novel gain
of function protein

INVERSION
- A region of DNA on the chromosome can flip its
orientation with respect to the rest of the
chromosome.

DELETIONS
- A large section of a chromosome can be deleted
resulting in the loss of a number of genes.

DUPLICATIONS
- Some genes are duplicated and displayed twice on the same chromosome

CHROMOSOME NON-DISJUNCTION
- During cell division, the chromosomes fail to successfully separate to opposite poles, resulting in one of
the daughter cells having an extra chromosome and the other daughter cell lacking one.
- Can occur at Meiosis 1 or 2 producing some gametes with 2 copies of one chr. = at fertilization when
coupled with the other parents copy totals 3.
- EG Down Syndrome.