Medical Genetic Overview Flashcards
Define the cell cycle
• The cell cycle is the lifespan of somatic cells.
It describes the sequence of cell growth and cell
division. Somatic cells continuously undergo cell division
The interphase represents the phase of
cell growth
the longest phase in the cell cycle.
The interphase
where several metabolic reactions take place.
takes place in the cytoplasm & the cell nucleus.
G1
cell grows in size
organelles replicated & after syntheses of enough ribosomes cells move to S phase.
If the cell can not divide again
, it enters G0
S
- cells replicate DNA
2n - 4n
Histone synthesis is linked to DNA synthesis
in S phase
G2 phase of cell cycle
Cell grows in size
- Synthesis of proteins associated with mitosis,
M phase of cell cycle
- mitosis
- Chromatin condenses - chromosomes, Cell death 4
segregate to opposite poles of the cell prior
to cytokinesis (cell division)
What dictates whether cells progress from
one cell cycle to the next?
Cyclin-dependent kinases (CdKs)
- Protein kinases
- phosphorylate specific proteins,
- 6CdKs
Cyclins - specify protein targets for CdKs to
phosphorylate
- Amounts of cyclins vary ín the cell cycle
- Decline in amount controlled by. l death
degradation in the 26s proteasome
Regulation of cell cycle progression
Cdk(s) and Cyclins
- Cyclins D and E (G1/S) activate
Cdk
• phosphorylate proteins in G1 that
will be needed for DNA replication
in S phase - Cyclin A (S phase)
• sustains DNA replication - Cyclin B (G2/M)
• regulates phosphorylation of
proteins in G2 - assures DNA
replication complete before cell
division.
Rb with regulated gene needed for DNA synthesis (…..)
What is phosphorylat the Rb?
E2F Transcription factor
D/Cdk4/6,
Mitosis
4 sub-phases:
1st - Prophase
2nd - Metaphase
3rd - Anaphase
4th - Telophase
followed by
Cytokinesis
Prophase
3 Major Events
1- chromosomes condense
2 - spindle fibers form (spindle fibers are specialized
radiating out from centrioles)
3 - chromosomes are
captured by spindle
Metaphase
chromosomes align along equator of the cell, with one kinetochore facing each pole
Anaphase
sister chromatids separate
spindle fibers attached to kinetochores shorten and
Pull chromatids towards the poles.
free spindle fibers lengthen- and push poles of cell apart
Telophase
• spindle fibers disintegrate
• nuclear envelopes form around both groups of chromosomes
•chromosomes revert to their extended state
- A single germ cell divides into four unique daughter cells.
Called
Meiosis
In meiosis, there
are 2 divisions
of the nucleus:
meiosis I
meiosis II
Crossing over
of homologous chromosomes in prophase 1 is exchange of part of genetic material between homologous chromosomes, switching parts of them forming recombinant chromosomes, allowing genetic variation in gametes.
Morphologically chromosomes are classified according to the position of the centromere
Centrally localized:
…..
Terminally localized:
Intermediate position:
METACENTRIC I
ACROCENTRIC
SUBMETACENTRIC
• the gene sequence is always
written
5’ → 3’
coding sequence (……..)
are interrupted by
noncoding DNA (……..).
exons
introns
Gene Expression
Definition: It is the process by which the information
encoded in a gene converted into protein
It briefly consists of 2 major processes,
First DNA transcription to RNA, Then RNA translation
into proteins
Post Transcriptional Modifications of mRNA
1-5’ “Capping”: The cap is a 7-methyl-guanosine attached to the S’-terminal end of the mRNA.
This cap permits the initiation of translation and stabilize the mRNA.
2-Addition of a poly-A tail: about 40-200 adenine
nucleotides attached to the 3’-end. These tails help
stabilize the mRNAs against
Exonucleases and facilitate their exit from the nucleus.
3-Excision (splicing) of introns, and ligation of the exons.
Now, mature mRNA is ready to be transferred to the
cytosol where protein synthesis occurs on ribosomes.
tRNA processing
1- Excision of intron in the anticodon loop.
2- Excision of sequence at 5’- end
3-The acceptor arm: addition of sequence CCA to the 3’- end.
4- Bases modifications: Uracil is reduced to form dihydrouracil.
Uracil is methylated to thymine.
Pseudouridine is formed.
Dihydrouracil and pseudouridine are
unusual bases.
Targets for cyclin B/ Cdkl include
histone H1 and lamin
• Phosphorylation of H1
•Chromatin condensation into mitotic chromosomes as cells enter M phase
• Phosphorylation of lamin
• nuclear envelope disintegration, an event that occurs as cens enter M
Programmed cell death
apoptosis
Intrinsic pathway
pro-apototic and anti-apoptotic
Bcl2 - anti-apoptotic protein blocks activity of pro-apoptotic proteins Bax and Bak
→ Pro-apoptatic :Bax and Bak change mitochondrial membrane integrity, allowing release of cytochrome c
Release of cytochrome C triggers formation of an apoptosome complex that activates a procaspase (9) to a caspase (9, initiating apoptosis
P53 transcription factor - stimulates synthesis PUMA and NOXA; tie up BcL2, allows Bax and Bak to promote apoptosis.
Extrinsic pathway
•signal molecules (e.g. TNFa) binds to a cell surface receptor - the “death receptor”
•Causes recruitment of an adaptor protein that triggers activation of procaspase 8
•by proteolytic cleavage and association of mnonomer subunits
•subsequent activation of other caspases
•Also activates Bid which activates Bax and
Bak
• Growth factors inhibit apoptosis
through receptors and activation of the Akt
athway, inhibit Bad; Bad is another activator
+ Bax and Bak.
Protein attached to the centromere
Kinetochore
Number of sets of a chromosomes in cells
Ploidy
Strands of DNA wrap around a protein (histone) forming
……………..
Nucleosomes/coil together forming chromatin.
Chromatin loops and coils together forming supercoils,
Supercoils bunch together forming chromsomes.
Def of A Gene
• a specific DNA sequence that
contains genetic information
• information required to make a specific type of protein
• that information is stored in the
sequence on the ‘sense’ strand
