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