SnapShot: Nonhomologous DNA End Joining (NHEJ)

Double-strand breaks (DSBs) are serious genetic lesions that must be repaired to prevent catastrophic loss of chromosomes. In general, two classes of mechanisms exist for repairing double-strand breaks, homologous recombination (HR) or nonhomologous end joining (NHEJ). HR requires an identical (or nearly identical) template strand of DNA to mend a lesion whereas NHEJ repairs a double-strand gap in DNA without a homologous template (middle upper panel).NHEJ, however, is not entirely devoid of guiding information. Short stretches of complementary “microhomology” sequences (1–10 base pairs) often appear at repair junc-tions, suggesting that limited base pairing between two ends of a double-strand break is exploited during repair. Thus, NHEJ is guided entirely by information in the lesion, which makes NHEJ error prone in comparison to HR. Nonetheless, NHEJ is optimal and necessary for double-strand break repair during the cell-cycle stages (i.e., G0 and G1) when sis-ter chromatids are not available to guide more accurate repair by HR. Most notably, NHEJ is incredibly flexible in terms of its substrates and repair mechanisms. In this SnapShot, we describe the wide range of lesions on which NHEJ operates, the diverse mechanisms used to join these breaks, and the many outcomes possible at the repaired junctions.