GAG WK5 Flashcards
What is aneuploidy
abnormal number of chromosomes
Why is proper chromosome segregation important
it can lead to aneuploidy and lead to developmental disorders
What is crossover recombination
exchange of genetic material by forming physical links between homologous chromosomes
What is the purpose of crossover recombination
it helps chromosomes stay connected until they are pulled apart (ensures gamete receives 1 chromosome)
What is noncrossover recombination
the genetic exchange w/o forming physical links
What is the purpose of noncrossover recombination
it helps with chromosome alignment
What are the 4 types of recombination errors
- meiosis I non-disjunction
- meiosis II non-disjunction
- reverse segregation
- precocious sister chromatid separation
What happens in meiosis I non-disjunction
both homologous chromosomes go to the same pole (same cell) and fail to segregate
What is the result of meiosis I non-disjunction
- creates 2 types of gametes
- 2 gametes w/ an extra chromosome (disomic)
- 2 gametes w/ no copies of those chromosomes (nullosomic)
What happens during meiosis II non-disjunction
both sister chromatids go to the same pole (same cell) instead of segregating
What is the result of meiosis II non-disjunction
- creates 4 types of gametes
- 2 normal gametes
- 1 gamete w/ an extra chromosome
- 1 gamete w/ no copies of that chromosome
What happens during precocious sister chromatid separation
sister chromatids separate prematurely during meiosis I instead of waiting until meiosis II
What is the result of precocious sister chromatid separation
- one gamete lacks that chromosome entirely
- one game has an extra chromosome
What is the cause of precocious sister chromatid separation
- Errors in the cohesin proteins that hold sister chromatids together.
- faulty separase enzyme
What happens during reverse segregation
- sister chromatids are separated in meiosis I
- homologous chromosomes are segregated in meiosis II
What is the result of reverse segregation
- some gametes may have:
- an extra chromosome
- missing chromosome
- normal chromosome number (if error balances itself out)
What is trisomy
cell has 3 copies of chromosome
What is the syndrome associated with trisomy
Down Syndrome
What is monosomy
cell has 1 copy of chromosome
What is the syndrome associated with monosomy
Turner syndrome
What is a genetic marker
specific DNA sequence used to determine if mids-segregation happened in meiosis I or II
Why are genetic markers really useful
- genetic markers near centromeres
- don’t crossover during recombination
- makes thems reliable
What is the purpose of polar bodies
- researchers can trace back errors in chromosome segregation
- identify where mis-segregation happened
How are polar bodies useful i DNA analysis
- each polar body contains clues about chromosomal errors
- each polar body reflects specific stages of meiosis
What is nullosomy
a complete loss of one chromosome
Why is nullosomy problematic
there is a lack of genetic material for that chromosome
Why is trisomy problematic
an imbalance in gene expression because there is additional genetic material
What is a single mutation
results in a specific and single phenotype
What is a pleiotropic mutation
a single mutation causing diverse effects on phenotype
Why are pleiotropic mutations problematic
- it changes gene expression of multiple genes at the same time
- results in widespread disruption (ex: can affect heart, eye and liver)
What is sex chromosome aneuploidy
adding or losing sex chromosomes
TRUE OR FALSE: Sex chromosome aneuploidy are not survivable
FALSE
Name 2 examples of sex chromosome aneuploidy
- Turner Syndrome
- Klinefelter Syndrome
What is Turner syndrome
only have one X chromosome
What is Klinefelter Syndrome
an extra X chromosome in males (XXY)
What is Autosomal Monosomy:
loss of a single autosome
What is the main consequence of autosomal monosomy
always lethal (except for monosomy X)
Outline the relationship between aneuploidy and occytes and live birth rate
- high aneuploidy rate in oocytes (20%)
- only a small fraction make it to term (0.3%)
What is the chromsome number in Down syndrome
- 47 chromosomes
- extra chromosome on 21
What is the cause of Down Syndrome
non-disjunction
What are the features of Klinefelter syndrome
- increased height
- delayed/incomplete puberty
What is the relationship between motor age and aneuploidy
As a woman ages, the likelihood of her eggs (oocytes) having chromosomal abnormalities increases
What is a proteome
complete set of proteins in a cell or organism
Why does the proteome vary
- different cells express unique sets of proteins based on their function
- different mRNA transcripts undergo alternative splicing leads to different protein variant
What is the function of mass spectrometry
to identify proteins in a sample on a mass scale
How does mass spectrometry work
- proteins are broken down into shorter peptide sequences
- peptides are turned into gas (changing their charge)
- peptides go through a detector which measures their mass to charge ratio
What is the function of gene cloning
to copy a specific gene by inserting it into a plasmid
How does gene cloning work
- target gene is inserted into the plasmid and introduced into the bacteria
- bacteria replicates, amplifying the gene and producing target proteins
- tags can be added to genes for tracking protein
What is the function of fluorescent tags in gene cloning
- visualises where the protein is located in the cell
- tracks protein interactions and helps understand its role
What are post-translational modifications
polypeptide chains can be cleaved after translation and create multiple protein isoforms from the same mRNA
Name an example of post-translational modification
cleavage in insulin
What are the 3 main processes in insulin cleavage
- signal peptide
- formation of proinsulin
- cleavage to active insulin
What does signal peptide do in the cleavage of insulin
- signal peptide is added onto precursor protein
- it directs the precursor protein (pre-proinsulin) to the ER
Outline the formation of proinsulin
- in the ER, signal peptide is removed
- disulfide bonds form between A and B chains
- allows proper folding and formation of pro-insulin
Outline the cleavage to active insulin
- the C chain is removed
- only A and B chains are held by disulfide bonds
- mature insulin only consists of those 2 chains
- they are stable and functional for blood glucose regulation
Name an example where proteins cleavage goes wrong/problematic
- BACE overexpression leads to abnormal cleavage of APP into amyloid plaques
- contributes to Alzheimer’s disease
What are the 2 types of post-translation modifications
- glycosylation
- phosphorylation
Outline the process of glycosylation as a type of post-translation modification
adds sugar units (glycans) to proteins to create side chains
What is the function of glycosylation in post-translation modifications
helps localise proteins to specific cell areas & stabilises proteins in bloodstream
Outline the process of phosphorylation in post-translation modifications
it adds phosphates and changes the protein conformation
What is the function of phosphorylation in post-translation modifications
activates or deactivates proteins which are involved in transmitting signals in pathways
Name 2 ways post-translational modifications can be detected
- Western Blots
- mass spectrometry
How do western blots detect post-translational modifications
- they use antibodies designed to recognise specific modifications
How does mass spectrometry detect post-translational modifications
- by detecting mass or charge shifts in protein fragments
- can use antibodies or fluorescent tags
What is ubiquitination
a post-translation protein modification where a small protein (ubiquitin) is attached to lysine residues on other proteins
What is the function of ubiquitination
tags proteins for degradation but can also change the protein’s activity + location + stability
What is the Ubiquitin-Proteasome System
a system of enzymes (E1, E2, E3) that add chains of ubiquitin to the protein marking it for breakdown by the proteasome
What is the proteasome
large protein complex where degraded proteins are processed
How does the Ubiquitin-Proteasome System degrade proteins
- cap proteins remove ubiquitin tags, unfold proteins and use ATP to guide the protein into the proteasome core
- they have a cylindrical core that contains enzymes that cleave the proteins into short peptides
What happens after the proteins are broken down by the proteasome
proteins are broken into smaller pieces for reuse or disposal by the cell
What is the Purpose of Ubiquitination and Proteasome-Mediated Degradation
- maintains protein quality by removing degraded or misfolded proteins
- regulates protein levels
What is the function of CDKs
regulate cell cycle and promote cell division
What are cyclins
- proteins that activate CDK
- Each cyclin pairs with specific CDKs to regulate distinct phases of the cell cycle
Why do certain cyclin-CDK complexes add ubiquitin tags to themselves and other proteins
- regulates protein expression
- ensures proper cell cycle progression
What happens when mutations disrupt ubiquitination machinery in cancer?
can lead to rapid cell proliferation, genomic instability, and cancer development
What are the consequences of rapid cell proliferation caused by disrupted ubiquitination?
uncontrolled growth of cells
How does genomic instability contribute to cancer?
It increases mutations and errors in DNA replication.
How does altered signalling contribute to tumorigenesis?
t promotes cancer development.
What are the main steps in ubiquitination profiling?
- Capture methods: Isolating ubiquitinated proteins using beads or antibodies.
- Analysis: Fragmentation and mass spectrometry to identify ubiquitination levels.
What is the purpose of ubiquitination profiling in cancer research?
- understand ubiquitination’s role in cancer progression
- identify potential therapeutic targets
What is lysosomal degradation?
A protein breakdown process where lysosomal enzymes degrade proteins, organelles, or pathogens
What is the function of lysosomal enzymes?
to break down proteins and nucleic acids
How does lysosomal degradation differ from ubiquitination-mediated protein breakdown?
- Lysosomal degradation involves enzymatic digestion within lysosomes
- ubiquitination tags proteins for degradation by the proteasome
What happens when lysosomes become leaky with age?
Lysosomal contents can escape, causing significant cellular damage.
What are stress granules?
membraneless organelles that form in response to cellular stress, storing RNA and proteins to provide temporary protection
Can stress granules permanently fix lysosomal leaks?
No, they temporarily seal lysosomal leaks but are not permanent solutions
How does lysosomal dysfunction contribute to ageing?
By impairing cellular function and triggering stress responses
How is lysosomal dysfunction linked to neurodegenerative diseases?
Accumulation of damaged proteins disrupts neuronal function, contributing to diseases like Alzheimer’s and Parkinson’s
Why is the combination of lysosomal dysfunction and persistent stress granules harmful?
It exacerbates cellular damage, promoting ageing and neurodegenerative disease progression.
