Lecture KH8. chromosomes Flashcards
what is different between the genomes in bacteria and the genomes in eukaryotes?
The genomes in bacteria are independent single circular molecules
The genomes in eukaryotes are made of a characteristic number of independent linear DNA molecules
what form do chromosomes always exist?
as a DNA/protein complex called Chromatin.
what is the key feature of chromatin? When is that key feature at its maximum?
It is condensation/compaction
DNA molecules are highly packed/coiled
The maximum compaction happens during metaphase, to be able to distribute the chromosomes to the daughter cells
What is the difference between Metaphase and Interphase?
Metaphase - Highly condensed for transmission to daughter cells. No DNA replication. No transcription (it’s packed too tight to be able to do anything)
Interphase - This is the real functional chromosome, undergoing replication and transcription. This is where the action is.
what are the topological domains in chromatin?
They are these loops, which are characteristic features of the interface nuclei/ chromatin.
The DNA contained in these loops do not interact with each other, forming a sort of physical separation
The gene regulatory events are different in each topological domain, the genes are different as well
what separates the topological domains?
the boundary element, DNA that is not organized in the same way, it has properties that tend to isolate what is happening inside the domains
what do they dark and light bands in chromatin condensation
dark = topological domains
light = boundary elements
What have polytene chromosome puffs shown regarding chromatin organization?
It shows that the organization of chromatin is dynamic, with the decondensation happening during transcriptional activation
When the genes are needed, the chromosomes decondenses, unwinds further than the state it was in, active transcription then takes place in these “puffs”
what is the karyotype
it is the chromosomal complement of a species.
the chromosomes are independent, tightly packed and have characteristic arms
there is a regular set of chromosomes for each species, and sometimes sex-specific
what are somatic cells?
In summary, somatic cells make up the majority of an organism’s body and are crucial for its growth, development, and maintenance, but they are not involved in reproduction or passing genetic material to the next generation.
What can chromosome rearrangement (breaks / translocation ) causes when it happens in somatic cells?
It can cause diseases, particularly cancer
How do we get cancer? (with the example of leukemia in mind)
the generation of a new DNA sequence at the junction between the 2 chromosomes / 2 genes. It created a fusion gene that was never meant to be. This fusion disrupts the growth control in the blood cell lineage (in the example of leukemia) which gives rise to cancer.
What can chromosome rearrangement (breaks/translocation) causes when it happens in germ cells?
it would give rise to gametes with variant chromosomes
which can go to the next generation
HOWEVER the offsprings made from that variant have reduced fertility
which makes these rearrangement usually a dead end
This is why it is hard to breed different species together , because the chromosomes don’t match
if it still manages to get through, it can lead to the evolution of the karyotype
what are the 3 elements required for replication and stable inheritance of linear chromosomes ?
- origin of replication
- centromere
- 2 telomere (ends)
what did the experimental discovery in yeast prove regarding the origins of replication?
- autonomously replicating sequence (ARS) are required for plasmid replication
- In presence of ARS, plasmid replication occurs, but mitotic segregation is faulty!
how to improve mitotic segregation?
you need a centromere, centromeric sequence! to get proper exponential growth
what is the kinetochore?
it is an organelle attached to the centromere and to which the spindle microtubules are attached
how do centrosome sequences and microtubules link together?
The centrosome sequences have common sequences that are long enough to form 1 nucleosome,
which can recruit a centrosome-specific histone variant CENP-A (centrosome protein A)
CENP-A recruits the microtubules for mitosis:
- CENP-A recruits the CBF3 protein complex
- CBF3 recruits Ndc80 complex which connects to the microtubules
how do you change a circular molecular into a linear molecule?
You cut it using a restriction enzyme
Does a plasmid with ARS and CEN that works well as an experimental circular chromosome in yeast also work well as a linear chromosome ?
NO, because a molecule with ordinary ends is unstable
HOWEVER
it is possible to clone the ends of that linear molecule from the ends of chromosomes, telomeric sequences (telomeres) and now it is stable and is able to replicate
What are the 3 main roles of telomeres?
- protect from exonuclease
- prevent end-to-end fusion
- solve a replication problem faced by linear DNA
what is the telomere problem?
when the replication fork comes to the end of the leading strand you need to make an RNA primer on the lagging strand , and then extend the DNA
BUT
that last RNA primer is unstable, it is going to be degraded which shortens the chromosome
this is an unsustainable practice as it will lead to the loss of the essential gene
What is the solution to the telomere problem?
telomerase! a DNA polymerase
how:
Telomeres have simple repeat DNA sequences for humans it is (TTAGGG)
It lengthens the leading strand with these telomere sequences
Telomerase is a reverse transcriptase that carries its own RNA template that is complementary to the telomere repeat so (AAUCCC) in humans
it will add 3 bases and then SLIP and continue to add more, it adds 6 bases at a time
by extending this end it can help overcome the shortening problem
why is telomerase only active in germ and stem cells but not somatic cells?
somatic cells divide only a few times, so existing telomeric repeats are long enough
