DNA Repair Flashcards
What are Mutations?
Permanent change in DNA sequence
What types of mutations are essential for evolution?
Silent & Non-Silent mutations
How can DNA become damaged?
- Radiation
- Mutagens
- Replication errors
How many proteins does the human genome encode for dedicated to DNA repair?
More than 130
What are FOUR mechanisms for DNA repair in cells?
- Mismatch Repair
- Base-Excision Repair
- Nucleotide-Excision Repair
- Direct Repair
Who is recognised for their work in Mismatch DNA Repair?
Paul Modrich
What does Mismatch DNA Repair do?
Fixes replication errors & improves accurary 100-1000 fold
What is Mismatch DNA Repair based on?
Distinguishing old and new strands
How does Mismatch DNA Repair work in E. coli?
Methylation on Adenine within GATC
What are the steps in Mismatch DNA Repair?
- Mut S complex binds to mismatched base pair
- Mut L binds to Mut S
- Mut L / Mut S complex moves along DNA until it finds a Mut H bound at hemimethylated GATC sequence
- Mut H is an endonuclease that cleaves unmethylated strand
This triggers repair
Mutations in which proteins causes colon cancer?
MutS & MutL
(MSH Proteins)
Who is known for their work in Base Excision Repair?
Tomas Lindahl
Which enzymes recognise lesions in DNA?
DNA Glycosylases
What are the steps in Base Excision Repair?
- Generates apurinic or apyrimidinic (AP) site
- AP site cut by endonuclease
- Segment of DNA is replaced by DNA Pol I using its 5’-3’ endonuclease activity
- Ligation of DNA strands (DNA Ligase)
Who is known for their work with Nucleotide Excision Repair?
Aziz Sancar
What are Nucleotide Excision Repair needed for?
Lesions that distort helix
- UV: pyrimidine dimers
- Cigarette smoke: benzo-pyrene guanine
What enzyme complex does Nucleotide Excision Repair use?
Multi-subunit enzyme complex: Exinuclease
How does Exinuclease work?
Hydrolyses phosphodiester bonds on either side of distortion
What is Xeroderma Pigmentosum (XP)?
Inherited condition where nucleotide excision repair is inactive
- Sunlight sensitivity (pyrimidine dimers)
- Susceptible to melanoma
When is Direct Repair used for DNA repair?
When there is no removal of bases or nucleotides
Where does Direct Repair occur?
In bacteria and yeast
What causes Direct Repair?
Damage by alkylating agents
What is the impact of DNA damage encountered during DNA replication?
- Unrepaired lesion encountered; replication stalled
- Replication fork may collapse
- Other repair pathways engaged
How is Homologous Recombination repair mediated?
- BRCA2 and the RAD51 recombinase
- Requires another DNA strand
How is Non-Homologous End Joining (NHEJ) mediated?
- DNA-dependent protein kinase and DNA ligase IV complex
- Modify and re-join DNA ends
Error Prone
Dysfunction in which DNA repair mechanism causes susceptibility to skin cancer?
Inactive nucleotide excision repair
Dysfunction in which genes cause breast cancer?
BRCA1 and BRCA2
DNA repair of double stranded breaks
Mutation or inactivation of which tumour suppressor protein is a marker in many cancers?
p53
Mutation or inactivation of which tumour suppressor protein is a marker in many cancers?
p53
How is Poly-ADP Ribose Polymerase used in DNA repair and cancer therapy?
- Crucial for detecting DNA strand breaks and other DNA damage in human cells
- Synthesises poly ADP ribose polymer at site
- Signal for recruitment of repair machinery
