DNA Replication Errors & Errors In Mitosis Flashcards
What is aneuploidy? Give an example of aneuploidy and the disease it results in.
Error in cell division that results in the daughter cells having the wrong number of chromosomes.
Trisomy of chromosome 21 - Down’s syndrome
Why does aneuploidy of sex chromosomes have less adverse effects than with autosomal aneuploidy?
There is variation in the number of X and Y chromosomes between males and females anyway
What can the effect of trisomy in the sex chromosomes result in?
Infertility
What can cause aneuploidy?
Anaphase lag
Non disjunction
What is nondisjunction? What cells does it result in? Can it happen in mitosis or meiosis?
Where both copies of a chromosome go into 1 daughter cell
Results in cells with one copy too many and 1 copy too few
Both mitosis and meiosis
Which chromosomes are used in chromosome analysis?
Metaphase chromosomes from an actively dividing cell
A karyotype can be displayed in which two ways?
A visual spread of chromosomes grouped by size/shape
Written notation
What would the karyotype for a normal male be?
46,XY
What would the karyotype for a Down’s syndrome female be?
47,XX,+21
If non disjunction happens in the first post-zygotic division which sort of karyotype will be produced?
Non-mosaic karyotype
Monosomy is only viable for life in which case?
A female with one X chromosome
If non disjunction occurs after the first post zygotic division which sort of karyotype will be produced?
A mosaic karyotype will be produced
What is mosaicism?
The presence of two or more cell lines in an individual
If non disjunction happens in meiosis 1, what will be the effect on the four daughter cells?
50% trisomy
50% monosomy
(All affected)
If non disjunction happens in meiosis 2 what will be the effect?
50% normal
25% trisomy
25% monosomy
What is more important in contributing to genetic diversity; random assortment or crossing over?
Both equally important
What is the difference between anaphase lag and nondisjunction?
Anaphase lag results in 1 normal cell and 1 monosomic cell
Nondisjunction produces a trisomic and monosomic cell
What is a Robertsonian translocation?
Happens between two acrocentric chromosomes, results in the breaking of each chromosome at the centromere and the two longer arms forming a new chromosome and the two shorter arms forming a chromosome (which is usually lost)
DNA damage can be separated into which 2 categories?
Endogenous
Exogenous
Give 4 examples of exogenous causes of DNA damage.
Ionising radiation
Alkylating agents
UV light
Anti-cancer agents
Give two examples of endogenous causes of DNA damage?
Dna replication errors
Free radicals
What checkpoints exist to repair DNA damage? What happens at these checkpoints to allow time for repair?
G1 checkpoint
G2 checkpoint
Checkpoint in mitosis
Temporary cell cycle arrest
If dna damage is too high or persists what two mechanisms are used to prevent the DNA damage resulting in cancer?
Apoptosis
Senescence = permanent cell cycle arrest
By which 2 methods can DNA DSBs be repaired?
Homologous-directed repair
Non homologous end joining
What does non-homologous end joining involve?
KU70/KU80 protect ends
Proteins recruited
Ligation of two broken ends back together
What are two types of homology directed repair?
Single strand annealing
Synthesis dependent strand annealing (SDSA)
What happens in the single strand annealing method of repairing DNA DSBs?
Break repaired - leads to deletions
What happens in the SDSA method of repairing DNA DSBs?
Uses identical DNA molecule to rebuild/repair itself
Uses DNA polymerase
What is meant by intra-tumour heterogeneity? What does it result in?
Different sub-clones within the same tumour
Tumour evolution and drug resistance
What is often seen when using chemotherapy drugs on a heterogenous tumour? What are the disadvantages of using chemotherapy on a tumour with regards to tumour evolution?
Initial shrinking of the tumour and then further expansion of resistant sub clones of the tumour (comes back worse and is now resistant)
The chemotherapy itself can cause mutations, some of which could give advantageous resistance mutations –>further evolution
How does cisplatin work as a cancer drug?
Causes dna damage in cancer cells by forming cross-links
What is the main consequence of the shortening of telomeres?
Cell death/ageing
How is the progressive shortening of chromosomes and telomeres prevented?
Telomerase aids in the replication of the ends of chromosomes and prevents chromosome degradation
What is a problem that can arise from the ‘non homologous end joining’ repair of DSBs?
More than 1 DSB close together may result in the wrong ends being joined together
What is chromosomal translocation? What can it result in?
Rearrangement of parts between non homologous chromosomes
Gene fusion
What is chromosome inversion? How does it occur?
Where a segment of a chromosome is reversed end to end
A single chromosome undergoes breakage and arrangement within itself
At which point of the cell cycle do non dividing cells enter G0?
At a point in G1 called the restriction point.
Which organelle is important in ensuring the accuracy of chromosome segregation?
The mitotic spindle
What is the structure of the mitotic spindle?
Part of the cell cytoskeleton - made of microtubules
What is the function of a centrosome? How many of them are in each cell? Where do they travel in mitosis?
Organises the microtubules in the cell cycle
2 in each cell
To opposite poles of the cell
The mitotic spindle is a proven target for successful treatment of…
Cancer
What is the chromosome status of most cancer cells?
Most cancer cells are aneuploid and show chromosome instability
Most cancer cells are aneuploidy and have increased copies of certain chromosomes, this results in increased expression of…
Oncogenes
What is the result of an increased number of centrosomes? In which cells are amplified chromosomes normally found?
Multipolar spindles are formed that promote chromosome instability
Cancer cells
If cancer cells often show amplified centrosomes, how are only two cells still produced in cell division? How can these mechanisms be exploited in cancer treatment?
Cancer cells have mechanisms to cluster these amplified chromosomes to produce two cells with aneuploidy
Inhibiting centrosome clustering in cancer cells —> in cell death and a possible cancer treatment with less side effects as it is specific to cancer cells
In which stage of mitosis is there a cell cycle checkpoint? How is this checkpoint ‘passed’?
Metaphase
Checkpoint passed if all chromosomes are attached to the mitotic spindle
What is cohesin?
The molecular glue that holds sister chromatids together, made from 4 proteins and makes a ring structure with dna
What is the loading and offloading of cohesin regulated by?
Cohesin control proteins
