DNA Damage and Repair Flashcards
What are the causes of DNA Damage?
Replication Errors
Chemicals
Radiation
Fill out the following diagram about DNA repair mechanisms
Chemical Damage
Types
Deamination
Depurination
Base Adducts
Base Alkylation
Chemical Damage
What is Deamination?
Transition of C/G to T/A during replication
Chemical Damage
Causes of Deamination
Nitrous Oxide
Spontaneous
Chemical Damage
What is Depurination?
Hydrolysis of the N-glycosyl linkage producing a basic site in the DNA
Chemical Damage
What is the effect of Depurination?
Deoxyribose lacking Adenine and Guanine bases
Chemical Damage
What is produced when tobacco is burnt?
Benzo[a]pyrenes or Polycyclic Aromatic Hydrocarbons
Chemical Damage
What is Benzopyrene converted to inside the body?
Epoxides
Chemical Damage
What effect can Epoxides have on DNA?
Base Adducts: Form bulky attachment onto the DNA
Chemical Damage
What happens when Epoxides are replicated?
DNA Polymerase replaces Adenine opposite Guanine instead of Cytosine
Chemical Damage
What effect does Nitrosamine have on DNA?
Nitrosamine is produced by tobacco
Base Alkylation: Alkylation of Guanine which interferes with replication
Physical Damage
Types
Ultraviolet Radiation
Ionizing Radiation
Physical Damage
Effect of UV Radiation
Cross-links adjacent pyrimidines on same DNA strand forming pyramidine dimers
Typically, a dimer forms between two Thymines
Physical Damage
Effect of Ionizing Radiation
Causes Double-Stranded Break
Replication Errors
Types
Transition: Replacement of base with base of same category (i.e. purine with purine or pyramidine with pyramidine)
Transversion: Replacement of base with base of another category (i.e. purine with pyramidine or pyramidine with purine)
When may Insertions and Deletions occur?
Insertions and Deletions: Non-homologous end joining
Deletions: Replication Errors
What happens if DNA Damage occurs?
Apoptosis
DNA Mutation
What are the stages of DNA Repair?
Removal of Damage
Replacement of Damage
What are the types of DNA Damage Repair?
Mismatch Repair
Nucleotide Excision Repair
Base Excision Repair
Double Stranded Break Repair
Mismatch Repair
What is replication mismatch?
Replication Errors escaping proofreading
Mismatch Repair
Which protein is involved in mismatch repair?
Mut proteins
Mismatch Repair
What are the steps of Mut protein activity?
Identify strand with mismatch
Repair procedure
Mismatch Repair
What are the steps of mismatch repair?
Endonuclease removes mismatched nucleotides + additional nucleotides
Pol III fills gap using ssDNA
DNA ligase joins ends
Nucleotide Excision Repair
When is it used?
UV radiation forming DNA dimers
Nucleotide Excision Repair
Procedure
UV specific endonuclease identifies dimer
Cleaves DNA segment containing dimer
Gap filled using DNA polymerase and ligase
Base Excision Repair
When is Base Excision Repair used?
When bases are lost spontaneously
Deaminated, Alkylated or Methylated
Base Excision Repair
Procedure
DNA Glycosylase cleaves nitrogenous base with damage
Endonuclease cleaves sugar and phosphate
Polymerase fills gap and ligase joins ends
Double Stranded Break Repair
What may cause double stranded breaks?
Ionizing Radiation
Oxidative Free Radicals
Chemotherapeutic Drugs
Double Stranded Break Repair
Types
Non-Homologous End Joining
Homologous Recombination
Double Stranded Break Repair
What is Non-Homologous End Joining
Joining of two cut ends
May cause mutation
Double Stranded Break Repair
What is Homologous Recombination?
Between Homologous Chromosomes
Causes no loss of DNA as sister chromosome used as template
Occurs in late S or G2 phase
Examples of diseases caused by mutation in DNA repair genes
Breast and Ovarian Cancer
Hereditary Nonpolposis Colorectal Cancer/Lynch Syndrome
Xeroderma Pigmentosum
Mutation of Repair Genes
Breast Cancer
Mutation of BRCA1 and 2 genes increase risk
Mutation of Repair Genes
Lynch Syndrome
Mutations of Mut genes allowing accumulation of mutations
Causes tumors in colon
Mutation of Repair Genes
Xeroderma Pigmentosum
Mutation affecting nucleotide excision repair pathway
Causes sensitivity to UV light