DNA and Chromosomes - MCB L4 Flashcards
Give the 4 phases of cell cycle, in order
G1, S, G2, M
What happens during the G phases?
The cell grows e.g. ATP accumulation
Which phases comprise interphase?
G1, S, G2
Centrosomes
Things at each pole of cell
Centriole
Organelle inside centrosome that releases spindle
Centromere
Between sister chromatids
Give the stages of M phase in order
Prophase, Prometaphase, Metaphase, Anaphase, Telophase, Cytokinesis
Telomeres
Repeating, non-coding sequences at ends of chromosomes to protect chromosome by protecting coding sequences
Kinetochore
Intimately associated with centromere. Spindle fibres join to kinetochore.
Prophase
Nucleolus disappears. Chromosomes condense. Mitotic spindles form from centrosomes.
Prometaphase
Nuclear membrane disintegrates. Centrosomes move to opposite poles. Kinetochores form and spindle attaches to kinetochores.
Metaphase
Chromosomes align at equator
Anaphase
Sister chromatids separate, centromeres split in two. Now called chromosomes. Pulled towards opposite poles.
Telophase
Chromosomes arrive at poles. Spindle breaks down. Nuclear envelope reforms
Cytokinesis
Cytoplasm divides resulting in two genetically near-identical cells. All other components e.g. Golgi are randomly assigned between cells as they can make whatever they lack
What molecules regulate cell cycle? How do they regulate it?
Protein kinases and cyclins; they regulate the cell cycle through a series of phosphorylation and dephosphorylation reactions.
If something is sensed to be wrong in the cell cycle, what occurs?
Cell cycle stops or cell dies (apoptosis)
What may occur if the control mechanisms in cell cycle fail?
Cancer
Which phases do chemotherapy drugs target? What side effect does this have?
S and M phases. This means that rapidly replicating cells such as hair cells are killed
If not enough ATP in a cell to divide, what happens?
The cell cycle is paused: the control mechanisms signal to ‘wait’
What happens in S phase?
DNA replication
What happens in M phase?
Nuclear division and cell division
The breaking of the triphosphate bond in nucleotides is useful for what reason?
Provides energy for formation of covalent phosphodiester bond between nucleotide and next nucleotide
What is the benefit of having multiple replication forks?
Allows for genome to be copied far quicker
What are the names of the two parts of the replication fork?
Leading strand, lagging strand
Leading strand. What kind of synthesis?
3’ end moving towards fork. Continuous synthesis
Lagging strand. What kind of synthesis? Why does it have gaps? What are the fragments called?
3’ end moving away from fork. Discontinuous synthesis. DNA polymerase works in 5’ to 3’ direction. So once it has polymerised one part of strand, a new bit has appeared nearer to fork. So polymerase rejoins nearer to fork, leaving gaps and making double stranded Okazaki fragments. Gaps filled by DNA ligase.
DNA primase
Adds an RNA primer, a foothold for polymerase to bind to. Primer is on both strands.
Nuclease
Removes primer after polymerase has synthesised DNA. Also removes damaged DNA/ wrong nucleotides.
DNA ligase
Comes in after nuclease. Tidies up, connects fragments
Is DNA primase more active on one strand than the other? Why?
More active on lagging strand as it has to keep adding more primers.
Werner Syndrome
Arises from mutation in DNA helicase. Errors in DNA replication and DNA repair. Cells replicate slower so start to show diseases found in elderly.
Name two methods of preventing accumulation of mutations
Proof-reading capacity of DNA polymerase. Excision repair systems.
Proof reading capacity of DNA polymerase
During DNA replication, DNA polymerase is proof-reading the strands. If wrong nucelotide inserted, the position of the free 3’ end of the nucleotide is changed so next nucleotide cannot bind so DNA polymerase stalls, preventing mutation. Wrong nucleotide removed by nuclease.
Excision repair systems
Throughout cell life, they repair any damage to DNA
What internal sources can damage DNA?
Products of normal cell function. Cell produces oxygen free radicals and hydrogen peroxide
What external sources can damage DNA?
Mutagenic chemicals (benzene, cigarette smoke), UV, ionising radiation
Synonymous SNP
No change in amino acid sequence due to SNP, so function of protein unchanged so not associated with disease state.
Non-synonymous SNP
Change to amino acid sequence due to SNP so function of protein changed so associated with disease state.
Somatic mutation
Bad for the individual, affects a particular cell type.
Germ line mutation
Affect every cell in offspring
What are monogenic genetic diseases?
Diseases arising due to a single gene disorder
Name 3 examples of monogenic genetic diseases, stating what type of mutation is responsible for each and whether the disease is associated with loss or gain of function
Substitution: Sickle-cell anaemia. Loss of function. Deletion: Cystic fibrosis. Loss of function. Insertion: Huntington’s disease. Gain of function
Sickle Cell Disease
Due to single nucleotide substitution in HBB gene (beta-globin chain of haemoglobin). Haemoglobin molecules become sticky, leading to sickle shaped RBCs. Die quickly, so causes anaemia, and clogs up capillaries
Cystic Fibrosis
3 base pair deletion in CTFR gene which causes protein to not be transported properly so not expressed on outside of cells. The protein is a transmembrane protein involved in chloride transport. So messes up chloride transport particularly in lungs so abnormal mucus leading to infection. Impaired chloride transport so loss of function
Huntington’s disease
Insertion. Neurogenerative disease. Due to increase in number of CAG repeats in HTT gene. HTT gene is expressed in nerve cells. CAG encodes glutamine and polyglutamine and polyglutamine is sticky so polyglutamines stick together to make a toxic product which kills nerve cells
What determines the severity of Huntington’s disease and how early you will get it?
The number of CAG repeats; the more polyglutamine the more toxic the gene.
How is Huntington’s disease a gain-of-function mutation?
Because of the production of a toxic molecule.
