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Lecture 15

BIOB11H3 Lecture Notes - Lecture 15: Primase, Transcription Factor Ii H, Enzyme


Department
Biological Sciences
Course Code
BIOB11H3
Professor
Dan Riggs
Lecture
15

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BIOB11: Molecular Aspects
65
Lecture 15: Telomere Replication & DNA Repair Processes
Telomere
-series of short repetitive DNA sequences located at the ends of eukaryotic chromosomes
-eukaryotic chromosomes are composed of linear dsDNA
End-Replication Problem
-DNA polymerases can’t reach end of lagging strand and
remains unreplicated
-happens on all newly synthesized strands
-incomplete 5’ ends if allowed to persist, gradually shorten
the length of chromsomes such that essential regions
eventually would be compromised
Overhanging Strand
-Overhanging strand loops and invades to prevent
nucleases from binding
>invasion is base-pairing oftelomeric repeat (
-Telomere capping proteins bind to loop to protect the end
Telomeric Repeats
-simple repetitive sequence
-in vertebrates: ~5’TTAGGG3’, repeated
500 to 5000 times
-Telomerase: enzyme/RNA complex
1.) Enzyme contains RNA complementary
to end of G-Rich strand and binds to it.
2.) RNA serves as template for addition of
nucleotides on 3’ end
3.) After a segment of DNA is synthesized,
telomerase RNA slides to new end
4.) Telomerase elongates further from new
end and gap in complementary strand is
filled by replication enzyme complex
polymerase-alpha and primase
*all done to maintain end repeat and loop
Incomplete 5 ends: If allowed to
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BIOB11: Molecular Aspects
66
Consequences of Reduced Telomerase Activity
1.) Loss of essential genetic material
2.) Fusion of ends of uncapped chromosomes
>chromosome fusion produces another centromere for the chromosome
-called dicentric
-leads to breakage when segregation occurs
DNA Repair
-DNA polymerases have 3 activities:
> 5’ to 3’ synthesis: synthesis function
> 5’ to 3’: primer removal
>3’ to 5’ exonuclease: proofreading function
Exonucleases
-all 3 polymerases have a 5’ to 3’ exonuclease activity (primer removal)
>removes primer to replace with DNA
-all 3 polymerases possess 3’ to 5’ exonuclease activity (proofreading)
>removes mismatched bases on growing 3’ strand
*Pol I uses exonuclease function to remove primer, then polymerase function to synthesize
new DNA
Properly Paired Region
Mis-matched Regions
-repair processes are activated by altered
geometry
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