B2.064 Prework 1 Mechanisms of DNA Damage Flashcards
what is the difference between a mutation and DNA damage?
DNA damage results in mutations only if it is NOT repaired
damage is routine (physical, chemical, copying errors)
describe somatic vs germline mutations
somatic: only affects individual
germline: mutations in cells that produce gametes
what are the 2 types of chemical mutagens?
reactive chemicals
free radicals
how do reactive chemicals damage DNA?
adds chemical moiety to DNA (DNA adducts)
often alters base pairing
can produce DNA ds breaks
describe the mechanism of reactive chemical EMS
electrophilic agent that transfers alkyl groups to DNA
causes G to pair with T
describe the mechanism of DNA cross linking drug cisplatin
forms both intra and inter strand cross links
replication stalls
product double stranded breaks
differentiate between UVA and UVB damage
UVA
-less damaging but can penetrate deeper
-generates ROS
UVB
-wavelength in range of max absorbance of DNA
-3-4x more effective per dose than UVA
-generates ROS and damaged DNA directly by breaking covalent bonds
what is the first line of defense for UV protection
chromophores in skin (melanin)
how does UV light damage DNA?
produces thymidine dimers
what happens when thymidine dimers are encountered?
DNA replication can:
- stalls and is either repaired or not
- continues without base pairing
- employ special DNA polymerase that evolved to tolerate T-T
what is the effect of ionizing radiation on DNA?
ss and ds breaks
what is the effect of infection mutagens on DNA?
insertional mutagenesis- viruses
disrupt protein coding
cause ds breaks
change gene transcription
how are mistakes fixed during replication?
3’ to 5’ exonuclease on DNA polymerase complex
