Week 1 DNA repair pathways Flashcards
What are the three single nucleotide damage repair pathways?
Mismatch repair, base excision repair, nucleotide excision repair
What are the three double strand DNA break repair pathways?
Homologous recombination, non-homologous end joining, and interstrand crosslink repair
What is the mechanism of mismatch repair?
Mismatch proofreading proteins scan newly replicated DNA, detects nick in new strand, removes section of replicated daughter strand, repair DNA synthesis
Lynch syndrome is a disorder of what DNA repair pathway?
Mismatch repair
What types of errors does base excision repair correct?
Small lesions
What types of errors does nucleotide excision repair correct?
Large, helix distorting regions
What is the mechanism of base excision repair?
DNA glycolase removes altered base pair, AP endonuclease (5’) and lyase (3’) are recruited and remove 1-4ish nucleotides, DNA polymerasefills the gab, DNA ligase seals the gap
Xeroderma pigmentosum is a disorder of what DNA repair pathway?
Base excision repair
What are the clinical manifestations of Lynch syndrome?
Hereditary colon cancer
What are the clinical manifestations of xeroderma pigmentosum?
1000-fold increase of squamous/basal cell carcinomas
What is the mechanism of xeroderma pigmentosum?
Mutation in any one of 8 XP genes causes a dysfunctional nucleotide-excision DNA repair complex, which prevents repair of pyrimidine dimers that are formed as a result of ultraviolet light exposure.
What is the mechanism of homologous recombination?
ATM recognizes dsDNA breaks, recruits repair proteins (including BRCA1/2), crossing over/strand inversion occurs, DNA is re-synthesized creating two copies of corrected sequence
What is the mechanism of non-homologous end joining?
Ku heterodimers recognize dsDNA breaks, recruit DNA protein kinase to align breaks, limited repair synthesis and ligation usually involving base pair deletions
Ataxia telangiectasia is a disorder of which DNA repair pathway?
Homologous recombination
BRCA1/2 dependent inherited cancers are disorders of which DNA repair pathway?
Homologous recombination
Werner syndrome is a disorder of which DNA repair pathway?
Homologous recombination and crosslink repair
Fanconi anemia is a disorder of which DNA repair pathway?
Non-homologous end joining
Bloom syndrome is a disorder of which DNA repair pathway?
Non-homologous end joining
What are the clinical manifestations of ataxia telangiectasia?
Ataxia (loss of control of body movements), telangiectasia (widening of veins), immunodeficiency, extreme sensitivity to radiation, predisposition to malignancy
What is the mechanism of ataxia telangiectasia?
Mutation in ATM gene leads to inability to recognize dsDNA breaks, so repair complex is never recruited and cell can progress through the cell cycle with damaged DNA
What is the mechanism of BRCA1/2 dependent inherited cancers?
BRCA 1/2 are part of homologous recombination repair complex; dsDNA repair is defective
What are the clinical manifestations of Fancomi anemia?
Short stature, developmental abnormalities, bone marrow disorders, cancer (especially leukemia)
What is the mechanism of Fancomi anemia?
Mutation in one of 12 possible FANC genes (regulate interstrand DNA crosslink repair)
What are the clinical manifestations of Werner syndrome?
Short stature, premature aging, cancer
What is the mechanism of Werner syndrome?
Mutation in WRN gene (DNA helicase used in homologous recombination and DNA replication)
What are the clinical manifestation of Bloom syndrome?
Short stature, narrow face, skin sensitivity to sun, SLE-resembling butterfly rash, immunodeficiency, cancer (especially leukemia), possible intellectual disability
What is the mechanism of Bloom syndrome?
Mutation in BLM gene (DNA helicase used in homologous recombination and DNA replication)
