Lecture 7b Flashcards
When do somatic cells stop losing telomere length?
Senescence
What protein complex protects telomeres from damage?
Shelterin
How can oncogenically active cells bypass senescence?
Loss of p53 check point
How is the telomere lasso formed?
Annealing the the G-rich strand to the small region of C-rich strand
Where is telomerase constitutively expressed?
Germ line cells
Oncogenically transformed cells that have bypassed the p53 checkpoint can survive crisis if they express what?
Telomerase
What percentage of cancer cells express telomerase?
85%
How does telomerase help cancer cells surpass the Hayflick Limit and achieve biological immortality?
Increased telomerase activity allows for indefinite proliferation
After how many divisions do normal cells enter crisis?
About 20
Why does lagging strand synthesis stall at chromosome ends?
No place to lay down a new RNA primer
What kind of enzyme is telomerase?
Reverse transcriptase
What does telomerase add, and to which end of which strand?
Telomere repeats to the 3’ end of the lagging strand
What are the two essential subunits of telomerase?
hTR and hTERT
What does hTERT stand for?
Human telomerase reverse transcriptase
What is hTERT composed of?
The protein catalytic subunit
What does hTR stand for?
Human telomerase RNA
Where does hTERT bind on the DNA?
3’ end of G-rich strand overhang
What is hTR?
The RNA template for telomerase
What protein regulates telomerase?
Shelterin
What do long telomeres form?
Closed loop that inhibits telomerase activity and DNA repair
What do short telomeres form?
Open formation that induces telomerase or p53 depending on cell
In addition to protecting the ends of chromosomes, what other function do telomeres perform?
Act as a sensor to overall DNA damage in a cell
How do the 15% of cancers that don’t express telomerase achieve immortality?
Via Alternative Lengthening of Telomeres (ALT)
Which proteins can alternatively lengthen telomeres?
RAD 51-52
Increasingly unstable genomes within a tumor leads to what?
Intratumor heterogeneity
Where are telomeres the longest?
Muscle, brain, and gametes
Where are telomeres shorter?
Stomach, blood cells, liver, and kidney
Mutations in the protein or RNA components of telomerase can cause what disease?
Dyskeratosis Congenital (DKC)
In what age does DKC develop, and what do its symptoms resemble?
5-15 year olds, resembles premature aging
What is the function of GRN163L?
Inhibits telomerase growth, telomere synthesis, and cell growth
What is glycosylation?
Normal enzymatic process in which sugars are added to proteins or lipids
What is glycation?
Non-enzymatic attachment of sugars to proteins or lipids
What causes glycation?
High blood glucose levels
What are advanced glycation end products (AGEP) associated with?
Premature and excess wrinkling and aging; damage to blood vessels, skin, kidneys, brain
hTERT extends the G-rich strand by how many nucleotides?
6
