DNA mutation and repair

Rate of mutation

probability of anyone base changing 2×10^-8 per base pair per generation

Mutation frequency

incidence of loss of function mutation in a specific gene

10^-5 per person in population using dominant or X-linked

Spontaneous mutation

mistakes/changes that happen regardless of the environment

e.g., wobble base pairing or tautomers of base inserts wrong base

e.g., strand slippage gives insertion or deletion

inaccurate crossing over btwn homologous chromosomes during meiosis

chemical instability of DNA bases

i) depurination - loss of purine base from sugar - leaves apurinic site

ii) demaination of bases -NH2 to =O, leaves mispaired base pair C → U or Cmethyl → T most common

Induced mutation

-chemical or physical cause of DNA change

a. interaclators- inset in DNA, insertions or deletions

b. ionizing radiation- causes breaks and base oxidation, 8-oxo-G oxidized base can basepair with A

c. UV light- cuases thymine dimers

Proofreading during DNA replication

catches 99% of initial mutations

Mismatch repair

mop up of DNA polymerase mistakes

Base Excision repair

enzyme recognizes odd base (e.g. U, oxo-G) or mispaired G-T base pair

-enzyme removes that one base (break base-sugar bond), then sugar, and allows DNA polymerase to repair

Nucleotide excision repair

recognizes distortion in DNA, e.g. thymine dimers or modified bases

similar to mismatch repair but acts at any time in cell cycle

specializes on bulky additions to DNA or thymine dimers that distort the double helix

One protein scans for lesions in DNA

Cuts out a length of DNA in one strand

DNA polymerase replaces the removed strand

Photoactivated repair

direct repair of thymine dimer-photolyase enzyme in bacteria

uses blue light to provide energy to split dimer bonds

common in organisms

NOT in placental animals

SOS repair bacteria

error prone but last chance

finds replacement templates from other copies of DNA in cell instead of other strand