BIOL 3110 Lecture Notes - Lecture 4: Eukaryotic Dna Replication, Unknot, Telomere
Wednesday, May 18, 2016
DNA replication, Telomeres and Telomerase
BIOL 3110
Announcements:
-First midterm is scheduled on May 25th (next Wed.)
-Midterm covers Lecture 1 to end of eukaryotic DNA replication, but not telomeres 9on
next midterm)
-Bring an eraser, extra pencils, and a calculator for all exams (midterms and final)
Recap of last lecture:
Function of DNA topoisomerases:
1. Remove or introduce supercoils
2. Decatenate or catenate DNA
3. Unknot or knot DNA
!1
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Wednesday, May 18, 2016
DNA topoisomerases:
-Topoisomerases cut, move one (or two) DNA strand(s) relative to the other, and re-
ligate (re-seal) DNA -> This will change linking number
-Some topoisomerase are really important in the cell and there are many versions in
our cells so it is unlikely that you will have no topoisomerase
-In simpler organisms with smaller numbers of topoisomerases, if you delete them or
mutate them, they are dead
•That is why using topoisomerase inhibitors was to cripple the topoisomerase in
cancer cells specifically
-In example we see that is a Type IA topoisomerase
!2
find more resources at oneclass.com
find more resources at oneclass.com
Wednesday, May 18, 2016
•All of them have a tyrosine residue at catalytic site which bonds with phosphoester
bond and actually cuts a phosphoester bond and links to the phosphate group
-Depending on whether you link to phosphate on 5’ C or 3’ C you get Type A vs.
Type B topoisomerases
-Recall: Type A links to the 5’ C phosphate while Type B links to phosphate-tyrosine
linkage from 3’ end
•This forms a cut
•For this particular case (TypeIA), it also has another part of the enzyme that grabs
the other end and pulls it through, and after it pulls it through you just reverse the
reaction and basically re-ligate the DNA
•Type IB doesn’t pull the strand through, but it allows the DNA strand to swivel so it
essentially changes the linking number (one at a time)
•Each time you change the linking number, you go through a cut, pull the strand
through and re-ligate (and repeat)
-Type II topoisomerase:
•They generally come as dimers
-The dimers (each of them) will cut a single strand so together they cut the double
strand
-They form a 4 bp stack
•What has to happen first
before you re-ligate the
DNA in order to change
the linking number?
Another duplex has to pass
through this
-Type I activity at the DNA
level:
•Type IA changes Lk one at
a time and only relaxes -ve
supercoils
!3
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
First midterm is scheduled on may 25th (next wed. ) Midterm covers lecture 1 to end of eukaryotic dna replication, but not telomeres 9on next midterm) Bring an eraser, extra pencils, and a calculator for all exams (midterms and nal) Function of dna topoisomerases: remove or introduce supercoils, decatenate or catenate dna, unknot or knot dna. Topoisomerases cut, move one (or two) dna strand(s) relative to the other, and re- ligate (re-seal) dna -> this will change linking number. Some topoisomerase are really important in the cell and there are many versions in our cells so it is unlikely that you will have no topoisomerase. In simpler organisms with smaller numbers of topoisomerases, if you delete them or mutate them, they are dead: that is why using topoisomerase inhibitors was to cripple the topoisomerase in cancer cells speci cally. In example we see that is a type ia topoisomerase.
