Nonhomologous end-joining

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Fig. 1. Proteins in DNA repair pathways. DNA repair proteins are listed for each of the following pathways BER (Base Excision Repair), NER (Nucleotide Excision Repair), MMR (Mismatch Repair), HR (Homologous Recombination), and NHEJ (Nonhomologous End Joining). PARP1/2 and BRCA1/2 are relevant in BER and HR pathways, respectively.

DNA repair pathways can be divided into those that respond to SSB and those that respond to DSB. SSB repair pathways include base excision repair (BER), mismatch repair (MMR), and nucleotide excision repair (NER). DSB repair pathways include nonhomologous end joining (NHEJ) and homologous recombination (HR). The proteins involved in these DNA repair pathways are shown in Fig. 1. 

Mutations mainly originate from limited fidelity of DNA replication and DNA damage. Additionally, nonhomologous end joining (NHEJ) during repair of doublestrand breaks also leads to mutagenesis. 

Figure 22.19. Mechanistic models for the formation of chromosomal aberrations. Regions of sequence homology (e.g., repeats and pseudogenes) are shown as black boxes with the arrow indicating orientation. HR, homologous recombination NHEJ, nonhomologous end joining SSA, single-strand annealing.

Eukaryotic cells possess two pathways for the repair of DSBs. One pathway is homologous recombination and appears to be very similar to the one described above in E. coli. However, much less is known about the details of this pathway in mammalian cells. In yeast, homologous recombination is the major pathway for the repair of DSBs. In mammalian cells it is restricted to the late S and G2 phases of the cell cycle. The second pathway is called nonhomologous end joining (NHEJ), and it is thought to be the major pathway for the repair of DSBs in mammalian cells. The two pathways differ in the proteins that participate in them, and they also significantly differ in the outcomes they produce. Homologous recombination produces few errors, whereas NHEJ is error-prone. 

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