Double-strand breaks cause genomic instability and are thus potentially lethal to cells. They also greatly increase the risk of cancer and the chance of chromosome structural mutations

Question

Compare and contrast the two mechanisms of double-strand break repair. Why would one mechanism be used over another?

Answer 1

Two mechanisms have evolved to carry out double-strand break repair.
Non-homologous end joining (NHEJ) is an error-prone repair process that repairs double-strand breaks occurring before DNA replication. If a double-stranded break damages a eukaryotic chromosome during G1 of the cell cycle, replication of the damaged chromosome is blocked. Completion of NHEJ produces an intact DNA duplex and allows replication across the repaired region in the upcoming replication cycle, but the repair is often imperfect because resection removes nucleotides that cannot be replaced. While NHEJ is error prone, it prevents more extensive loss from degradation of unprotected ends. Mutations can be generated, however, when nucleotides are lost by transcribed genes.
Synthesis-dependent strand annealing (SDSA) is an error-free process that repairs double-strand breaks occurring after the completion of DNA replication. When a double-strand break (DSB) affects one sister chromatid, the other chromatid is intact. The strand invasion process displaces one strand of the duplex and creates a displacement (D) loop. DNA replication within the D loop synthesizes new DNA strands from intact template strands, and the sister chromatids are reformed by dissociation and annealing of the nascent strand to the other side of the break. By accomplishing the removal of DNA in the immediate vicinity of a double-strand break and the replacement of the excised DNA with a duplex identical to that in the sister chromatid, SDSA carries out error-free repair of double-strand breaks.
To summarize, non-homologous end joining is an error-prone system for the repair of double-strand DNA breaks that occur before S phase. Synthesis-dependent strand annealing takes place after completion of the S phase and uses the identical sister chromatid as a source of the template strand sequence to synthesize a replacement duplex in an error-free manner.