Lecture 20 - Chromosome Structure Flashcards
What is the karyotype of the parent organism ?
Where the organised representation of all the chromosomes in a eukaryotic cell at metaphase, the chromosomes are lined in in their pair from 1-22 to XY at the end.
How many copies of a chromosome does a diploid eukaryotic cell contain ?
2 copies
What do individual chromosomes occupy ?
Distinct subnuclear territories even in interphase nuclei.
What is a chromosome?
A higly coiled fibre iof chromatin.
What does interphase chromatin look like in an electron microscope?
Resembles ‘beads on a string’, The beads are nucleosomes
What is the structure of 30nm chromatin fibre ?
A supercoiled array of nucleosomes
What is the core of nucleosomes ?
a protein core around which DNA is wound, like cotton on a bobbin
The protein subunits of the nucleosome are core histones
What is the protein core of a nucleosome’s structure like?
How does it help the regulation of chromatin structure and function ?
The N-terminal tails of the 8 core histone subunits project out from
the nucleosome core and are free to interact with other proteins,
facilitating regulation of chromatin structure and function
What do linker histones do ?
Linker histones such as H1 strap DNA onto histone octamers
and limit movement of DNA relative to the histone octamer
- this facilitates the establishment of transcriptionally silent heterochromatin
How is DNA packaged by histone octamers ?
into a compact, flexible 30nm chromatin scaffold that can be remodelled to accommodate protein complexes involved in gene transcription and DNA replication
What is chromatin engineered to do ?
Chromatin is engineered to permit flexible responses to altered
transcription factor activity caused by changes in cell
differentiation status and changes in signalling pathway activities
What does interphase chromatin comprise of?
comprises a set of dynamic, “fractal globules”
(globules within globules) that can reversibly condense and decondense without becoming knotted
How are globules organised in order to benefit chromatin?
It is like a russian doll sorta thing.
At the nucleus level there are distinct patterns of chromatin
At a higher resolution we can see areas of open and closed regions forming these patterns
within those closed regions there are distinct patterns of chromatin and those are the fractal globules.
How does the globule organisation benefit chromatin?
It is fundamental to stabilisng the regions of inactive chromatin but also allows flexibility so that cells can react to certain cues such as progenitor cells differentiating into specialised cells.
What is found inside the nuclear periphery in interphase cells ?
Composed of transcriptionally inactive DNA (red)
RNA transcripts (green) are excluded from the periphery
What do the specialised DNA sequences contained in chromosomes facilitate?
reliable and complete DNA replication
segregation of duplicated chromosomes during cell division
What are telomeres and what do they do?
Specialised repetive DNA sequences at chromsome ends.
Telomeres define chromosome ends
and maintain chromosome integrity
What are telomeres replicated by ?
Replicated by a specialed DNA polymerase called Telomerase
Single-stranded 3’ overhanging TTAGGG repeat arrays are synthesised by the Telomerase enzyme and can be several hundred nucleotides long
What does chromosome segregation during cell division require ?
attachment of chromosomes to the mitotic / meiotic spindle
What do centromeres contain ?
Centromeres contain alpha-satellite DNA repeats – that readily form condensed chromatin with histone octamers containing unusual subunits
What is the difference between the Kinetochore inner and outer plate ?
Kinetochore Inner Plate proteins bind to chromatin containing alpha-satellite DNA
Kinetochore Outer Plate proteins bind to protein components of the mitotic spindle i.e. microtubules
Why do we need an inner and outer kinetochore ?
Part of the mechanism for ensuring faithful segregation of sister chromatids at cell division
How much of our DNA is coding DNA ?
1%
What is increasing biological complexity accompanied by ?
- increasing numbers of protein-coding genes
- increasing amounts of non-protein-coding DNA
- for regulating transcription and organising access
to protein-coding genes.
- for regulating transcription and organising access
What does cis-regulatory information determine ?
Some of the non-protein-coding DNA encodes cis-regulatory
information which determines where and when in the body adjacent
protein-coding genes are transcribed.
What are the 3 different types of repeated DNA sequences called Transposons ?
DNA Transposons
Retroviral retrotransposons
Non-retroviral polyA retrotransposons
How do DNA Transposons move ?
DNA transposons move by a cut-and-paste mechanism without
self-duplication, requiring the transposon-encoded enzyme Transposase
e.g. P-element (fly), Activator-Dissociator (maize), Tn3 / Tn10 (E. coli) DNA transposons are powerful mutagens
How do transposable elements like the retrovirus HIV produce new DNA copies and replicate ?
They replicate
via RNA intermediates, producing new DNA copies that integrate at new genomic locations, using self-encoded Reverse Transcriptase
They don’t fully encode active infectious virus
What are some examples of retrotransposons ?
Ty1-copia
Ty3-gypsy
ERV elements
How do non-retroviral, PolyA retrotransposons replicate ?
They are abundant in
vertebrate genomes and replicates via an RNA intermediate using
its own retrotransposon-encoded Reverse Transcriptase - copy & paste
What are some examples of non-retroviral, PloyA retrotransposons ?
Human L1 elements
(LINE-1 elements)
Human Alu elements
Mouse B1 elements
Long Interspersed Elements
“LINEs”
Short Interspersed Elements
“SINEs”
How are L1 reverse transcription products copied into a new gnome position ?
They are are integrated directly into the genome at new locations without the need to be packaged into a virus-like
particle
What happens is an L1 insertion disrupts genes ?
Some L1 insertions
are known to disrupt
genes and cause human
disease, e.g. Haemophilia
