DNA DAMAGE AND REPAIR
DNA Damage
DNA damage can lead to mutation if left unrepaired (genotoxic)
DNA damage (G-C to ethyl G-C), DNA mutation (G-C to A-T)
Alkylation of Bases
Process where electrophiles: encounter negative center, attack and add carbon alkyl group
N7 alkylation of guanine (X), N3 produce 3-methyl adenine that cannot base pair with other bases
stalling DNA replication (noncoding base), lead to mutation
ethylmethane sulfonate (EMS)
if cell attempt to replicate without damage repair
change base pair properties of a base (mutagenic)
Radiation
UV (low energy, formation of pyrimidine dimers) cyclobutane pyrimidine dimers (CPDs)
Gamma and xray (high E, form high reactive free radicals) alter bases and break strand
Pyrimidine Dimers
block DNA replication
wrong bases insert lead to mutation
form covalent bond in the same strand
DNA Repair
Directly undoing UV DNA Damage
repaired by CPD photolyase and (6-4) photolyase (catalyze repair of CPDs)
use energy from UV to blue light (break bond between 2 pyrimidine)
humans DNA damage from gamma and xray accept 06-methyl guanine methyltransferase as suicide enzyme
CPD photolyase
Excision Repair
remove most damage nucleotide and replace w fresh DNA
Base Excision Repair
act on subtle base damage
begins w DNA glycosylase
extrude a base, clip out the damaged base, leaves an apurinic site (attract DNA repair enzyme)
DNA repair enzyme
remove remaining deoxyribose phosphate, replace w nucleotide, ligase seal nick
Nucleotide Excision Repair
repair bulky damage distort DNA double helix
damaged DNA clipped by endonuclease, sites 12-13 nucleotides apart
recognize parental strand by methylated A
uvrABC endonuclease
DNA polymerase and ligase in action
Mismatch repair
methylated adenines determine parental strands
mutH, L and S introduce nick
exonuclease removed strand
DNA pol and ligase
Methyl transferase add CH3