Telomeres Flashcards
What is telomere? What is telomere structure and function?
- telomeres are positioned at the end of chromosomes
- confer stability on a linear molecule, protect chromosome ends, prevents fusion of chromosome ends, allow telomeres to be extended
what is the relative size of telomeres?
- vary from 2 - 20 kb in humans
- in human somatic tissues, telomeres shorten 50 to 100 bp per cell division
What is the meaning of tandem repeats at chromosome ends?
- repeated sequences that can be as large as 100 - 1000 repeats
- sites are CA rich at the ends
- the 3’ strand that overhangs is G/T rich and generates 14-16 bases of a single strand overhang (result of a specific limited degradation of a G/A rich strand on the 5’ end)
What happens to the CA-strand versus GT- strand?
- the C/A strand is degraded from the 5’ end to produce the G/T rich protruding 3’ end
What are differences between G-hairpins and G-quartets?
- the G hairpin is used as a primer
- the G quartet is 4 repeat units that are thought to interact through the remaining Gs to form a helical array at the end of the chromosome
what tissues do not have telomerase activity? where is it present in?
- most somatic tissues have no telomerase activity but is present in 90% of tumors
- often involved in immortalization of cells
what shows research promise in anticancer agents?
- telomerase inhibitors show promise as anticancer agents but must be careful not to harm tissues that have a high turnover rates of cell division
how can human cell lines be immortalized?
- many human cell lines can be immortalized by the introduction of the telomerase gene (hTERT)
- other tissue types require hTERT plus the SV40 T antigen to be immortalized
- normal tissues types can be transformed to onocgenic lines by introduction of hTERT, SV40 T antigen, and rasV12
what is the G quartet and how does this occur?
- guanine bases have an unusual capacity to associate with one another
- stacks of quartets of G residues
- each quartet contains 4 G.s that hydrogen bond with one another, forming a planar structure, following another 4 Gs from the next planar stacked below the first one
- connected via hydrogen bonds
What is D-loop versus T-loop?
- the D loop is a mechanism the mitochondrion uses to replicate itself
- the t-loop is a D-loop like structure that is the 3’ single-stranded end of telomere TTAGGG invades upstream region of telomere and displaces homologous repeats from duplex DNA
- enables no free ends on the tail of the telomere - the tail is paired with the homologous strand
What protein is crucial for the T-loop formation?
TRF2
- telomere binding protein makes complex with other proteins and stabilizes chromosome ends
What is the activity of RAP1?
- binds to the CA repeats at the ends of telomeres
When is the meiotic telomere cluster/bouquet formed?
Before synapsis/pairing of chromosomes during meiosis in many organisms
what is involved in the meiotic telomere cluster/bouquet?
Fibers that act across the nuclear membrane
What type of fibers are in the meiotic telomere cluster/bouquet?
Microtubules, actin or others
Why is telomerase needed?
needed to extend the ends of chromosomes to prevent degradation of useful genes
- in the gametes telomerase is used in order to prevent this degradation and pass genes onto offspring
Stn 1
protein keeps the degradation of the C/A strand from going too far
what is telomerase and its components?
- represents a solution to the replication of a linear template
- extends the 3’ OH end of the G/T strand - which acts as a primer
- contains a covalently attached RNA (192 bases) which serves as a template
- the template RNA contains 15-22 bases equivalent to 2 repeats of the CA rich repeating consensus
- acts as a specialized reverse transcriptase
Do somatic tissues have telomerase activity? Do tumor cells?
both have telomerase activity
What protein the Shelterin complex recruits Sir3/Sir4 proteins?
Rap1
What proteins bind histone H3 and H4 tails?
Sir3/Sir4
What protein facilitates formation of 30 nm and above fibers?
Sir3
What protein structure resembles lamin, a feature that helps it insert itself into the laminar matrix during formation of telomere bouquets?
Sir3
How can Drosophila acquire white patches within red eyes?
- genes transferred neat heterochromatin are sometimes silenced by spread of heterochromatin
- RAP1 binds C A/T repeats at telomeres
- SIR3/SIR4 bind to RAP1
- SIR 3/4 bind to H3/H4 tails
- SIR3/SIR4 polymerize
- SIR3/SIR4 attach to matrix
- white gene inactive = white patches
- white gene active = red patches
What is lamin?
matrix protein
Can telomerase keep cells young?
Telomerase prevents this decline in some kinds of cells, including stem cells, by lengthening telomeres
Is Arabidopsis survival affected by telomerase mutations and how?
Arabidopsis becomes progressively smaller and abnormal; does not survive past 10 generations
