1. Houston, we have a problem!
Chromosome erosion
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DNA polymerase I 5 3 3 5
growing
replication fork 3
DNA polymerase III 5
RNA 5
Loss of bases at 5 ends in every replication
chromosomes get shorter with each replication
limit to number of cell divisions? 3

2. Telomeres
Repeating, non-coding sequences at the end of chromosomes = protective cap
limit to ~50 cell divisions 5 3 3 5
growing
replication fork 3
telomerase 5 5
________________
enzyme extends telomeres
_________________________
different level of activity in different cells
high in stem cells & cancers -- Why?
TTAAGGG
TTAAGGG
TTAAGGG 3

3. Editing & proofreading DNA
Many different types of polymerases and nucleases
Cuts and removes abnormal bases
_____________________
repairs mismatched bases
Reduces error rate to 1 in 10 billion

4. DNA replication on the lagging strand
___________________________
serves as starter sequence for DNA polymerase III
HOWEVER short segments called Okazaki fragments are made because it can only go in a 5 3 direction 5 5 3 5 3 5 3 3
growing
replication fork 5 3
primase 5
DNA polymerase III
RNA 3

5. Replacing RNA primers with DNA
_________________________
removes sections of RNA primer and replaces with DNA nucleotides
DNA polymerase I 5 3
ligase 3 5
growing
replication fork 3 5
RNA 5 3
STRANDS ARE GLUED TOGETHER BY DNA LIGASE

6. Telomeres and Aging: Is there a connection?

7. What are telomeres? Telomeres are…
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They contain thousands of repeats of the six-nucleotide sequence, ____________
In humans there are 46 chromosomes and thus 92 telomeres (one at each end)

8. What do telomeres do? __________________________
They separate one chromosome from another in the DNA sequence

9. Telomere function, cont’.
Telomeres are also thought to be the "clock" that regulates how many times an individual cell can divide. Telomeric sequences shorten each time the DNA replicates.

10. Think of it like this….
Telomeres effectively "cap" the end of a chromosome in a manner similar to the way the plastic on the ends of our shoelaces "caps" and protects the shoelaces from unraveling.

11. How are telomeres linked to aging?
Once the telomere shrinks to a certain level, the cell can no longer divide. ________________________________________________________

12. What next?
So, scientists have determined that there is a direct connection between telomere length and aging. What was their next step?

13. What is telomerase, anyway?
Telomerase (TEE-LÓM-ER-ACE) is a ribonucleoprotein enzyme complex (a cellular reverse transcriptase) __________________________________________________________________________
It stabilizes telomere length by adding hexameric (TTAGGG) repeats onto the telomeric ends of the chromosomes, thus compensating for the erosion of telomeres that occurs in its absence.

14. How Does Telomerase Work?
Telomerase works by adding back telomeric DNA to the ends of chromosomes, thus compensating for the loss of telomeres that normally occurs as cells divide.
_______________________________________________________________________________________

15. How Does Telomerase Work?
In humans, telomerase is active in germ cells, in vitro immortalized cells, the vast majority of cancer cells and, possibly, in some stem cells.
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16. How Does Telomerase Work?
_____________________________________________________________________
Examples of immortal cells: cancer cells
Cancer cells do not age because they produce telomerase, which keeps the telomere intact.