Houston, we have a problem! Chromosome erosion __________________________________________________________________ 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

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

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

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

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

Telomeres and Aging: Is there a connection?

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

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

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.

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.

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

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

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.

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. _______________________________________________________________________________________

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. _________________________________________________________________________________________________________

How Does Telomerase Work? _____________________________________________________________________ Examples of immortal cells: cancer cells Cancer cells do not age because they produce telomerase, which keeps the telomere intact.