Double-strand breaks occur when the DNA double helix is completely broken in two. This can happen during replication or due to physical or chemical carcinogens. This damage poses a serious risk to the cell because it can lead to genome rearrangements. Multiple pathways can repair double-strand breaks, including non-homologous end joining (NHEJ) and homologous recombination (HR).
NHEJ uses a special ligase to join the two ends of the broken strand together. For this to occur, NHEJ looks for small regions of homology between the two single-stranded ends at the break sites. If the sequences from each end are complementary, the repair proceeds accurately. Mutations can be introduced if nucleotides were lost during the damage that caused the DNA strand to break. NHEJ is the predominant method for DNA repair throughout the cell cycle.
Unlike NHEJ, HR requires a template to process the repair. This is only found after the DNA has been replicated. HR utilizes the sister chromatid or a homologous chromosome as a template to restore the DNA sequence affected by a double-strand break. Due to the requirement for a template, HR is only used for DNA repair during the S/G2 phase of the cell cycle.
