Telomeres Problem
1. Essential in protecting information on
chromosomes
2. End replication problem recall
a. Have a leading and lagging strand on
both the top and bottom strand of DNA
b. Need available 3’ hydroxyl end for
extension of DNA
c. Removing the last RNA primer in a 5’ to
3’ strand to try to replace it with actual
DNA but we now have only a free 5’ end,
not a 3’ end. Thus can’t replace the code
d. Every time a cell divides, the
chromosomes get shorter because we
can’t fill in lagging strand’s sequence on
both ends
i. Aka attrition
e. This is due to humans having linear
DNA and not circular
3. Telomeres are like the aglet on a shoelace
4. They do not code for anything, are a buffer so
we lose telomeric DNA and not essential DNA
Hayflick Limit
5. Limitation to how many rounds of cell division we go through
6. The number of replications that can be done prior to reaching senescence
7. Critical Point: telomeres at a particular length, they’re not dead cells but they can
not divide anymore. Cells at a state of senescence
a. Cells not proliferating
b. Senile - showing a decline or deterioration of physical strength or mental
functioning, especially short-term memory and alertness, as a result of old
, age or disease.
c. Should be a permanent proliferation arrest
i. As opposed to quiescence, when a cell goes from G1 to G0, reverting
back to the cell division
d. Visual Hallmark: A physical change where cells spread out a bit more; we
can stain for this stage
e. Perhaps after 60 divisions, depends on the cell type
8. State of Crisis, Dysfunction
a. No telomeres at all and we do lose essential information
b. Can now have more mutations/dysfunction, impacted telomere stability →
inappropriate cell division now → increased likelihood of cancer
c. Visual hallmark: end to end fusions of terminal ends
d. Types of Dysfunctions
i. Dysfunction: sister chromatids fuse together, end to end
ii. Telomere Induced Foci (TIFS): telomere dysfunction, the spots you
see in microscopy, a medical scientific test
e. Could get a mutation in specific cells in some areas so they now express
telomerase and are replicating with bad DNA
Looking for Telomeres
9. Range in size
10. Looking at the terminus of a chromosome
11. Double strand and a G rich strand ending with a 3’ single-strand overhang
12. In humans, 5’ to 3’
sequence is TTAGGG; is G
rich
13. 3’ to 5’ sequence is thus C
rich
14. 3’ to 5’ end (C strand) will
end in AATC 80% of the
time; means creation is
not random
15. The structure looks like
damaged DNA
a. Like a single/double-strand break
b. Can lead to the initiation of a DNA damage repair pathway even though
the overhang is intentional, so we try to stop this repair
16. Stopping the repair is done by a collection of proteins called a Shelterin Complex
Shelterin Complex
17. that regulate possible telomere length extension by regulating telomerase and
1. Essential in protecting information on
chromosomes
2. End replication problem recall
a. Have a leading and lagging strand on
both the top and bottom strand of DNA
b. Need available 3’ hydroxyl end for
extension of DNA
c. Removing the last RNA primer in a 5’ to
3’ strand to try to replace it with actual
DNA but we now have only a free 5’ end,
not a 3’ end. Thus can’t replace the code
d. Every time a cell divides, the
chromosomes get shorter because we
can’t fill in lagging strand’s sequence on
both ends
i. Aka attrition
e. This is due to humans having linear
DNA and not circular
3. Telomeres are like the aglet on a shoelace
4. They do not code for anything, are a buffer so
we lose telomeric DNA and not essential DNA
Hayflick Limit
5. Limitation to how many rounds of cell division we go through
6. The number of replications that can be done prior to reaching senescence
7. Critical Point: telomeres at a particular length, they’re not dead cells but they can
not divide anymore. Cells at a state of senescence
a. Cells not proliferating
b. Senile - showing a decline or deterioration of physical strength or mental
functioning, especially short-term memory and alertness, as a result of old
, age or disease.
c. Should be a permanent proliferation arrest
i. As opposed to quiescence, when a cell goes from G1 to G0, reverting
back to the cell division
d. Visual Hallmark: A physical change where cells spread out a bit more; we
can stain for this stage
e. Perhaps after 60 divisions, depends on the cell type
8. State of Crisis, Dysfunction
a. No telomeres at all and we do lose essential information
b. Can now have more mutations/dysfunction, impacted telomere stability →
inappropriate cell division now → increased likelihood of cancer
c. Visual hallmark: end to end fusions of terminal ends
d. Types of Dysfunctions
i. Dysfunction: sister chromatids fuse together, end to end
ii. Telomere Induced Foci (TIFS): telomere dysfunction, the spots you
see in microscopy, a medical scientific test
e. Could get a mutation in specific cells in some areas so they now express
telomerase and are replicating with bad DNA
Looking for Telomeres
9. Range in size
10. Looking at the terminus of a chromosome
11. Double strand and a G rich strand ending with a 3’ single-strand overhang
12. In humans, 5’ to 3’
sequence is TTAGGG; is G
rich
13. 3’ to 5’ sequence is thus C
rich
14. 3’ to 5’ end (C strand) will
end in AATC 80% of the
time; means creation is
not random
15. The structure looks like
damaged DNA
a. Like a single/double-strand break
b. Can lead to the initiation of a DNA damage repair pathway even though
the overhang is intentional, so we try to stop this repair
16. Stopping the repair is done by a collection of proteins called a Shelterin Complex
Shelterin Complex
17. that regulate possible telomere length extension by regulating telomerase and
