DNA Repair and Cancer Flashcards
(26 cards)
What is ataxia telangiectasia?
What does this cause?
mutation in ATM gene
- Damage to the cerebellum»_space; difficulty with movement and co-ordination
- Weakened immune system
- UV light sensitivity
- DNA repair is disrupted > increases risk of cancer
Types of DNA damage
Single strand damage
Double strand damage
Mismatches
Deamination
Pyrimidine dimer
Cross linking
Exogenous sources of DNA dmage
Ionising radiation
Alkylating agents
Mutagenic chemicals
Anti-cancer drugs
UV light
What are alkylating agents?
Add alkyl group to guanine
Prevents strands of double helix bonding properly
Endogenous sources of DNA damage
Free radicals
DNA replication errors
What is ataxia telangiectasia due to?
Mutations in ATM gene
Failure of homologous directed repair
Define DNA replication stress
Inefficient replication that lead to replication fork slowing, stalling or breaking
What enzyme recognises DNA replication errors?
DNA polymerase
What enzyme removes DNA errors?
DNA exonuclease
What is fork slippage?
Wrong number of repetitive sequences
Cause of Huntington’s disease
- Replication errors due to fork slippage
- CAG repeats (37-80)»_space; neural degeneration
What is Huntington’s disease?
Autosomal dominant neurodegenerative disease
Degeneration of basal ganglia
Symptoms of Huntingon’s disease
Irritability
Depression
Small involuntary movements
Poor coordination
Difficulty speaking/swallowing
5 ways in which cells can respond to DNA damage
Cell cycle transitions
Apoptosis
Transcription
DNA repair
Senescence - cells become old
Types of single strand break repair
Base excision repair
Nucleotide excision repair
Mismatch repair
B ‘n’ M
Outline base excision repair
- deamination converts one base to another
- error is detected + incorrect base is removed
- base-less nucleotide is removed
- small hole is left in DNA backbone
- DNA polymerase fills hole with correct base
- DNA ligase seals gap
Outline nucleotide excision repair
- UV radiation produced base dimer
- error detected + surrounding DNA opens to form a bubble
- enzymes cut bubble out
- DNA polymerase replaces cut section
- DNA ligase seals backbone
Outline mismatch repair
- base is paired with incorrect base
- error is detected + DNA strand is cut (no bubble)
- DNA polymerase replaces cut section
- DNA ligase seals gap in backbone
Types of double strand break reapir
Non-homologous end joining
Homologous-directed repair
Outline non-homologous end joining
- broken ends are bound by protein complex
- another protein complex trims excess base pairs (resection)
- DNA ligase repairs break
- new DNA may not be exact copy of original piece + may be missing some bases»_space; downstream consequence
Outline homologous-directed repair
- DNA either side of break resected by a protein complex
- second complex allows a heteroduplex to formed > broken strand + unbroken intact template DNA combine
- displacement loop moves along DNA + makes a complementary strand to 3’ single strand template
- new DNA is captured by original strand
- DNA polymerase + ligase repair the break
What is a heteroduplex?
Two mismatched polynucleotide strands from two different parent molecules
Cause of Lynch syndrome
Defective mismatch repair
Caused by mutations in mismatch repair genes
Autosomal dominant
Lynch syndrome puts you at a high risk of what?
Colorectal cancer
Endometrial cancer
Gastric cancer
Ovarian cnacer
