Radiation Biology for Physical Scientists/Radiation Induced Damage and Repair

DNA helix courtesy of Jahobr

Structure of DNA

DNA helix is an organic ladder-like molecule with two strands of phosphate molecules as the backbone and four base molecules as the crosslinks: guanine (G),adenine (A),thymine (T) and cytosine (C). The biological damage of these lesions would depend on how the cell handles this damage.

Radiation-Induced DNA Damage

Exposure of cells to radiation leads to biological damage to the DNA molecule in the cell. This damage can take the form of damages to the base molecules or breaks in the phosphate strands. Damaged DNA matters because this can prevent genes from being correctly read or cause deletions that alter the type of protein produced.

Base Damages

Radiation can change the structure of DNA bases by damaging, destroyed or chemically modifying them.

Strand Breaks

The breaking of a DNA strand is assumed to occur when the absorbed energy in one sugar-phosphate volume in the DNA threshold exceeds a threshold of 17.5 eV. A single strand break (SSB) can occur on either one of the DNA strands. A double strand break (DSB) is assumed to form if two SSB's are produced on opposite strands of the DNA but within 10 base pairs. DSB's can be the result of a single particle track or two independent particle tracks.

DSB's can be quantified by pulse-field-gel-electrophoresis while SSB's can be quantified by comet assay.

DSB's are more damaging to DNA than SSB's and base damages but are also less common.

Increasing LET of radiation is consistent with increasing biological severity of the DNA damage. 
It is hypothesized that this is due to the higher density of ionizations associated with higher LET 
leading to clustered DNA damage.
  

Clustered DNA damage

Clustered DNA damage is a type of damage in which multiple DNA lesions are induced within a region of a few nm. It is produced where the density of ionization/excitation is high, whereas the isolated damage would be generated where it is low.

Repair of DNA Damage

Radiation induces large number of lesions in DNA wich must be successfully repaired before they can have an effect. The repair of DNA decreases with increasing LET of radiation.

For double-strand breaks

The repair pathway for double strand breaks depends on the phase of the cell's cycle.

Homologous Recombination Repair (HRR)uses a second undamaged DNA helix of similar base structure as a template for repair. This process occurs in the late-S/G2 phase of the cell cycle and is error-free.

Non-homologous end joining (NHEJ) is the rejoining of the two broken ends of the DNA by deleting some of the DNA. This process occurs in the G1 phase and is more prone to error. The possible loss of genetic code sequence in this process could be a source of oncogenic lesions.

For Single-strand breaks

A break in one strand is readily repaired using the undamaged parallel strand of the DNA with its complementary base.

For base damage

Base Excision Repair is the main "pathway" employed to remove radiation-induced damage to bases. The mechanics involves cleaving the damaged base and its replacement with an undamaged base through several steps including the excision of a section of the DNA sequence and its resynthesis using the complementary chain as a template.

References

Chaudhry MA. Base excision repair of ionizing radiation-induced DNA damage in G1 and G2 cell cycle phases. Cancer Cell International 2007;7:15. doi:10.1186/1475-2867-7-15. PMCID: 2063494