Sesh 4: DNA Damage and Repair Flashcards
What are cell cycle checkpoints?
Points in the cell cycle that check for DNA damage, and temporarily arrest the cell to provide time for DNA repair.
What is the most genotoxic type of DNA damage?
Double-strand breaks- difficult to repair, and if not repaired correctly than can cause mutations or cell death
What effect does the DNA damage/repair response have on carcinogenesis?
It acts to prevent carcinogenesis.
If get defects in DNA repair, can predispose to cancer.
What is Lynch syndrome?
Sufferers have a genetic defect in a mismatch repair gene, predisposing them to colorectal cancers as a result of DNA replication stress/damage.
What is intratumour heterogeneity and what does it promote?
Different sub-clones within the same tumour.
Promotes tumour evolution- therapy resistance and metastasis.
What is a driver mutation?
A change in the DNA sequence of a cell that alters the biology of it, and drives the progression of the cancer.
What are some problems with chemotherapy?
- Side effects
- Can itself induce mutagenesis- may select for a resistant sub-clone
- ->promotes tumour evolution and secondary tumours
What are 3 consequences of missegregation in meiosis?
- Causes 1/3 of all identified miscarriages
- Infertility
- Leading cause of mental deficits
What is aneuploidy?
An abnormal chromosome number.
What is non-disjunction?
Failure of 1/more homologous pairs of chromosomes (meiosis I) or sister chromatids(meiosis II/mitosis) to separate normally, resulting in daughter cells/ gametes with too many or too few chromosomes (aneuploidy).
What is the result if non-disjunction occurs in early development (1st few post-zygotic divisions) ?
- Monosomy cell line usually lost, unless it involves the X
- Other cell line e.g. = 47,+21…..Non-mosaic karyotype
What is the result if non-disjunction occurs in later cell divisions during development?
- Monosomy cell line usually lost, unless involves X
- Will result in a mosaic karyotype…some cells will have trisomy and some with normal
Define mosaicism.
The presence of 2/more cell lines in an individual.
Can be throughout the body or tissue limited.
What is anaphase lag?
Delayed movement of chromosomes in anaphase, where 1 homologous chromosome or chromatid fails to connect to the spindle or fails to be included in the reforming nucleus.
Results in aneuploidy.
What is the SRY gene, and what does it code for?
The sex-determining region, coding for a transcription factor needed for the initiation of male sex determination.
What is a karyotype?
The number and appearance of chromosomes in the nucleus of a somatic cell.
Can refer to a picture or notation.
Why may there be a problem producing the final Okazaki fragment on the lagging strand?
Last bit of replicated DNA may not be long enough to make a full fragment and ligase with another fragment. Therefore a telomerase elongates it by adding a telomere (C and G rich).
How might interfering with telomerases allow cancer treatment?
If inhibit DNA telomerase selectively in cancer cells, could prevent them replicating effectively, and would eventually lose coding sections of DNA (DNA shortens with each replication).
What is xeroderma pigmentosa?
A rare autosomal recessive disorder characterised by deficits in the ability to repair DNA damage due to UV radiation. Sufferers have mutations in nucleotide excision repair enzymes, so are highly sensitive to sunlight.
What does UV radiation usually do to DNA?
Forms pyrimidine dimers.
This is usually excised by endonucleases, DNA polymerase repairs the missing sequence, and ligase joins the strand= nucleotide excision repair.
In simple terms, what is non-homologous end joining?
A type of DNA double-strand break repair- broken ends are recognised, the damaged DNA is removes and 2 broken ends are ligated.
What is the potential problem with non-homologous end joining as a DNA repair mechanism?
May lead to errors, as the double strand breaks it repairs are not always clean breaks. The break ends are directly ligates, without the need for a homologous template for repair.
