Lecture 6 - DNA Replication and Repair Flashcards
Why is completing the lagging strand problematic on a linear template?
- When the primer nearest the end is removed there is no 3’ end to extend so as to replicate the end section
- Therefore the short remaining single-stranded region is removed
- This causes chromosome shortening that leads to cell death
Telomeres
Repetitive sequences a the ends of eukaryotic chromosomes. TTAGGG
Telomerase
Replicates chromosomal ends. It contains and RNA sequence as well as protein that synthesizes the last bit of DNA. The RNA molecule acts as template for priming the synthesis of the telomeric DNA sequence
Without the action of telomerase how many bp for chromosome ends lose?
50-200 bp
Aneuploidy
Abnormal numbers of chromosomes. Typically caused by chromosome segregation defects
Euploidy
Right number of chromosomes
Examples of structural abnormalities
Mutations, deletions, amplifications, and rearrangements of chromosome segments
What typically causes structural abnormalities?
DNA replication defects
Three repair mechanisms
- Proofreading
- Mismatch repair
- Excision repair
Proofreading
- Done by DNA Polymerase III
- It will detect if it added the incorrect nucleotide and immediately excises it and adds the correct one
Mismatch repair
- Template DNA us methylated (addition of -CH3 to some of the bases normally Cytosine)
- Newly synthesized DNA is not
1. Error in replication leads to mismatched base
2. Mismatch repair proteins excise the mismatched base and some flanking sequence
3. DNA Polymerase I replaces missing sequence on the unmethylated strand and DNA ligase seals the gap
Excision repair
- DNA damage recognized by excision repair machinery which is constantly scanning DNA for damaged bases
- Excision repair proteins excise the damaged base and some adjacent sequence
- DNA Polymerase I replaces missing sequence and DNA ligase seals the gap
